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Statistical Analysis Plan OncoMed Pharmaceuticals, Inc.

Study 59R5-003 (Phase 2 Portion)

A Phase-1b/2 Study of Tarextumab (OMP-59R5) in Combination with Etoposide and Platinum Therapy in Subjects with Untreated Extensive Stage Small Cell Lung Cancer

PINNACLE: Phase-1b/2 INvestigation of anti-Notch Antibody Therapy with Etoposide and Platinum Therapy in Small Cell Lung Carcinoma Safety and Efficacy

Sponsor: OncoMed Pharmaceuticals, Inc.800 Chesapeake DriveRedwood City, CA 94063Phone: 650-995-8200

Prepared by:SynteractHCR

Version Number DateVersion 1 01SEP2016Version 2 19SEP2016Version 3 23MAR2017

OncoMed Pharmaceuticals, Inc. Statistical Analysis Plan 59R5-003 (Phase 2) 23MAR2017

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TABLE OF CONTENTS List of Abbreviations ...................................................................................................................... 5

Definitions....................................................................................................................................... 6

1. Introduction ............................................................................................................................... 8

2. Study Objectives ....................................................................................................................... 8 2.1. Primary Objectives ........................................................................................................... 8 2.2. Secondary Objectives ....................................................................................................... 8 2.3. Exploratory Objective ...................................................................................................... 9

3. Study Design and Plan .............................................................................................................. 9 3.1. Blinded Treatment Phase ............................................................................................... 10 3.2. Follow-Up ...................................................................................................................... 11

4. Determination of Sample Size ................................................................................................ 11

5. General Analysis Considerations ............................................................................................ 15 5.1. Analysis Software .......................................................................................................... 15 5.2. Baseline Values .............................................................................................................. 16 5.3. Missing Values ............................................................................................................... 16 5.4. Subgroup Analyses ......................................................................................................... 16 5.5. Multiple Comparisons/Multiplicity ................................................................................ 16

6. Analysis Data Sets .................................................................................................................. 16 6.1. Analysis Populations ...................................................................................................... 17

7. Summaries of Patient Characteristics ..................................................................................... 18 7.1. Subject Disposition ........................................................................................................ 18 7.2. Protocol Deviations ........................................................................................................ 18 7.3. Demographics and Baseline Characteristics .................................................................. 18

8. Efficacy Endpoints .................................................................................................................. 19 8.1. Progression-Free Survival .............................................................................................. 19 8.2. Total Tumor Length ....................................................................................................... 21 8.3. Overall Response Rate ................................................................................................... 22 8.4. Duration of Response ..................................................................................................... 22 8.5. Sites of Progression ........................................................................................................ 23 8.6. Overall Survival ............................................................................................................. 23 8.7. Landmark Survival ......................................................................................................... 23

9. Exploratory Analyses .............................................................................................................. 24

10. Pharmacokinetic Endpoints .................................................................................................... 26

11. Safety Endpoints ..................................................................................................................... 27 11.1. Treatment Cycles and Dosing ........................................................................................ 27


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11.1.1. Dose Intensity ...................................................................................................... 27

11.1.2. Dosing Compliance ............................................................................................. 28

11.2. Adverse Events ............................................................................................................... 28 11.3. Clinical Laboratory Parameters ...................................................................................... 29 11.4. Vital Signs ...................................................................................................................... 30 11.5. Electrocardiogram Results ............................................................................................. 30 11.6. ECOG Performance Status ............................................................................................. 31 11.7. Immunogenicity ............................................................................................................. 31 11.8. Prior and Concomitant Medications ............................................................................... 31

12. References ............................................................................................................................... 31 Appendix A. List of Tables, Figures and Listings ........................................................................ 32

Appendix B. Table Shells ............................................................................................................. 44

Appendix C. Figure Shells .......................................................................................................... 101

Appendix D. Listing Shells ......................................................................................................... 106

FIGURES Figure 1. Enrollment, Progressions and Deaths over Time – Control Hazard of Progression of 0.1386 Beyond 9 months .......................................................................................................... 13

TABLES Table 1. Progression-Free Survival: Power for the Alternative Hypothesis ................................. 12

Table 2. Enrollment, Progressions and Deaths over Time – Control Hazard of Progression of 0.1386 Beyond 9 Months.......................................................................................................... 12

Table 3. Hazards for Piece-Wise Exponential Model of Progression Free Survival .................... 14

Table 4. Hazards for Piece-Wise Exponential Model of Overall Survival ................................... 14


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LIST OF ABBREVIATIONS

AE Adverse event ANCOVA Analysis of covariance ANOVA Analysis of variance ATC Anatomical/Therapeutic/Chemical (class) AUC Area under curve BMI Body mass index BSA Body surface area CRF Case report form CNS Central nervous system CR Complete response CSR Clinical study report CTCAE Common terminology criteria for adverse events DOR Duration of response DSMB Data Safety Monitoring Board ECG Electrocardiogram ECOG Eastern Cooperative Oncology Group EP Etoposide and platinum (therapy) ES-SCLC Extensive stage small cell lung cancer HR Hazard ratio ITT Intent-to-treat (patient population) KM Kaplan-Meier MedDRA Medical Dictionary for Regulatory Activities MTD Maximum tolerated dose N3RPI NOTCH-3-ralated PFS index NE Inevaluable (by RECIST criteria) ORR Overall response rate OS Overall survival PCI Prophylactic cranial irradiation PD Progressive disease PFS Progression free survival PH Proportional hazards PK Pharmacokinetics PP Per-protocol (patient population) PR Partial response RECIST Response evaluation criteria in solid tumors (version 1.1) SAE Serious adverse event SAP Statistical analysis plan SD Stable disease SLD Sum of longest diameters TEAE Treatment-emergent adverse event TFLs Tables, figures and listings WBR Whole brain radiation WHO World Health Organization


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DEFINITIONS

Adverse event Any untoward or unfavorable medical occurrence in a human subject, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease temporally associated with the subject’s participation in the research, whether or not considered related to the subject’s participation in the research, or any baseline conditions that worsened during the study.

Baseline value The last non-missing value recorded prior to the first dose of study drug.

Best overall response Patient’s best investigator-assessed RECIST response to treatment category recorded since the start of the treatment.

On study tumor assessments

Tumor assessments that meet the following criteria: 1. No gap of ≥91 days between successive tumor assessments among those on or prior to the on study tumor assessment. (Note: a tumor assessment for which “Not Evaluated” is entered into the database does not qualify as a tumor assessment.) 2. No prior initiation of non-protocol anticancer therapy.

Overall response rate The proportion of patients achieving a complete response or partial response to treatment.

Dose intensity The total dose (in mg) a patient actually received divided by the total dose (in mg) the patient should have received had there been no missed doses, dosing delays or dosage reductions.

Intent-to-treat population All patients randomized to receive study drug regardless of whether they actually received study drug and regardless of whether evidence is found indicating they failed to meet study inclusion/exclusion criteria or had other protocol violations.

Last contact date The last contact date is the latest assessment/visit date recorded on any of the following case report forms: Discontinuation, Hematology, Chemistry, RECIST Overall Response Tumor Assessments, Survival Follow Up, Study Drug Infusion, Etoposide Infusion or Platinum Therapy Infusion.

Non-Protocol Anti-Cancer Therapy

Non-protocol anti-cancer therapies used by patients during their participation in this study, if any, will be identified by the sponsor after review of relevant data listings.

Per-protocol population The subset of safety population who either (a) have at least one response evaluation on study, or (b) die prior to their first scheduled response evaluation.

Platinum Therapy / Platinum Choice

The physician’s choice of platinum therapy (cisplatin or carboplatin) was used as a stratification variable by the dynamic randomization system. Discrepancies, if any, between the platinum therapy used to stratify a patient’s treatment assignment and the platinum therapy actually administered during the study will be dealt with as follows. Platinum choice entered in the dynamic randomization system will be used in all efficacy analyses where platinum choice is included as a model


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effect. However, actual platinum received (as documented on earliest Platinum Therapy Infusion CRF [e.g., Cycle 1, Day 1]) will be used when calculating dosing compliance.

Randomization Date Although each patient’s randomization date was recorded by site personnel on the Informed Consent case report form (CRF), the actual randomization date substantiated by the dynamic randomization system used to make blinded treatment assignments will be used in all analyses including calculations of times to events such as OS and PFS.

Randomized Study Drug Tarextumab or placebo Safety population The subset of the intent-to-treat population who received at least

one partial dose of tarextumab or Placebo and who have at least one post-dosing safety evaluation (labs, vital signs or adverse events).

Treatment-emergent adverse event

An adverse event that starts or increases in severity any time after the first administration of any randomized study drug (i.e., tarextumab or placebo) up to 30 days following the last administration of any study drug.


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1. INTRODUCTION This document outlines the statistical methods to be implemented for analyzing data collected within the phase-2 portion of OncoMed Pharmaceuticals, Inc. Protocol 59R5-003 (A Phase-1b/2 Study of Tarextumab [OMP-59R5] in Combination with Etoposide and Platinum Therapy in Subjects with Untreated Extensive Stage Small Cell Lung Cancer), amendment 6 dated 22 April 2016. The purpose of this statistical analysis plan (SAP) is to provide specific guidelines from which the statistical analyses will proceed. Any deviations from this plan will be documented in the clinical study report (CSR). The definitive analyses of efficacy data for making statistical inference with respect to the objectives the Phase-2 portion of the study and the definitive analyses of safety data will be performed using data from a formal data cut taken planned to occur in April 2017. Randomized treatment assignments will be unblinded at that time. Any subsequent data analyses that may be performed to include data accrued into the database following the April-2017 data cut will be considered secondary efficacy and/or safety analyses.

Investigating the pharmacokinetics (PK) of tarextumab in combination with EP is an objective of this study, but a detailed analysis plan is outside the scope of this document.

Throughout this SAP, the terms patient and subject are used synonymously to refer to an individual who was enrolled to participate in the clinical trial.

2. STUDY OBJECTIVES

2.1. Primary Objectives The primary objectives of this study are:

Phase-1b portion: To determine the maximum tolerated dose (MTD) of tarextumab when administered on Day 1 of each 21 day cycle along with etoposide 100 mg/m2 on Days 1, 2 and 3 and cisplatin 80 mg/m2 or carboplatin to an area under curve (AUC) of 5 mg/mL/min on Day 1 in subjects with untreated extensive stage small cell lung cancer (ES-SCLC).

Phase-2 portion: To determine the improvement in progression free survival (PFS) resulting from the addition of tarextumab to etoposide and platinum therapy (EP) in subjects receiving first-line therapy for ES- SCLC. (Platinum therapy for the phase-2 portion was similar to phase-1b [i.e., cisplatin or carboplatin], but the cisplatin dose was changed to 75 mg/m2.)

Statistical analyses concerning the primary objective for the phase-1b portion of this study will not be addressed in this SAP.

2.2. Secondary Objectives The secondary objectives of this study are:

Phase-1b and -2 portions: To determine the PK of tarextumab in combination with EP in subjects receiving first-line therapy for ES-SCLC

Phase-1b and -2 portions: To determine the immunogenicity of tarextumab in combination with EP in subjects receiving first-line therapy for ES-SCLC

Phase-2 portion: To estimate the improvement in overall survival (OS), 12-month survival and overall response rate (ORR) resulting from the addition of tarextumab to EP in subjects receiving first-line therapy for ES-SCLC


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Phase-2 portion: To correlate the treatment effect in PFS, OS, 12-month survival and ORR resulting from the addition of tarextumab to EP in subjects with Notch3, Hey2, Hes1, Hey1 and Hes6 expression

Phase-1b portion: To determine the safety and tolerability of tarextumab in combination with EP in subjects who are receiving first-line therapy for ES-SCLC

Phase-2 portion: To compare the safety and tolerability of tarextumab in combination with EP relative to EP alone in all subjects who are receiving first-line therapy for ES-SCLC

Statistical analyses concerning the secondary objectives for the phase-1b portion of this study will not be addressed in this SAP.

2.3. Exploratory Objective An exploratory objective of this study is:

Phase-1b and -2 portions: To describe the changes in exploratory pharmacodynamic biomarkers, including Notch pathway related genes and proteins and circulating tumor cells following tarextumab treatment

3. STUDY DESIGN AND PLAN The following descriptions of the study design and plan were copied from the study protocol. Since this SAP only covers analyses planned for the phase-2 portion of the study, some portions of the study design and plan related only to the phase-1b portion were omitted intentionally.

The study consists of a phase-1b lead-in portion to determine the MTD of tarextumab in combination with EP for 6 cycles followed by treatment with tarextumab alone until unacceptable toxicity or disease progression. The initial dose escalations of tarextumab will be conducted with etoposide and cisplatin. The dose of tarextumab will not exceed 15 mg/kg. Following the establishment of the highest tolerable dose of tarextumab in combination with etoposide and cisplatin, a cohort of 6 subjects will be treated at this dose in combination with etoposide and carboplatin. Once the safety and tolerability of tarextumab at this dose is also confirmed with etoposide and carboplatin, the protocol will transition to a phase-2, multicenter, randomized, placebo-controlled portion comparing the efficacy and safety of tarextumab at the highest tolerable dose in combination with EP for 6 cycles followed by single agent tarextumab relative to EP alone for 6 cycles in subjects receiving first-line therapy for ES-SCLC. However, if a DLT is observed in 2 or more subjects in the cohort of 6 subjects treated with the highest tolerable dose of tarextumab with etoposide and carboplatin, a new cohort of 3 to 6 subjects will be enrolled at the next lower dose level of tarextumab with etoposide and carboplatin. The highest tarextumab dose that is tolerable with both platinum options will be used in phase-2 portion of the study.

In phase-2 portion of the study, subjects may be treated with cisplatin or carboplatin as determined by the investigator prior to randomization. Alteration to the choice of platinum therapy is not permitted once the subject is randomized.

Etoposide 100 mg/m2 will be administered on Days 1, 2 and 3 along with cisplatin 80 mg/m2 for phase-1b and 75 mg/m2 for the phase-2 portion of the study or carboplatin to an AUC of 5 mg/mL/min on Day 1 of every 21-day cycle for 6 cycles, tarextumab or placebo will be given on Day 1 of every 21-day cycle prior to the administration of EP.


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Subjects may continue one of the chemotherapy drugs if the other is held or discontinued prior to completing 6 cycles of EP and prior to disease progression. Subjects should continue EP alone for a total of 6 cycles if tarextumab is held or discontinued prior to the completion of 6 cycles of EP. Subjects may continue study drug if one or both of the chemotherapy drugs is held or discontinued prior to completing 6 cycles of EP and prior to disease progression.

The phase-2 portion of the study may commence after the safety and tolerability of the highest tolerable dose of tarextumab has been confirmed in both cohorts of subjects with etoposide and cisplatin/carboplatin during phase-1b. The highest tarextumab dose that is tolerable with both platinum options will be used in the phase-2 portion of the study. For example: if tarextumab at 15 mg/kg is tolerable with etoposide and cisplatin, but not tolerable with etoposide and carboplatin; and tarextumab at 12.5 mg/kg is tolerable with etoposide and carboplatin, then tarextumab at 12.5 mg/kg will be the dose used in phase-2. The phase-2 portion includes a blinded treatment phase and follow-up phase. It is a multicenter, randomized, placebo-controlled portion evaluating the efficacy and safety of tarextumab in combination with etoposide and platinum therapy in subjects with previously untreated ES-SCLC. Subjects may be treated with cisplatin or carboplatin as determined by the Investigator prior to randomization. Alteration to the choice of platinum therapy is not permitted once the subject is randomized.

Approximately 135 evaluable subjects will be enrolled to the phase-2 portion of the study. Evaluable subjects are those who received at least one dose of study drug (either tarextumab or placebo).

Version 1.1 of standard response evaluation criteria in solid tumors (RECIST) criteria [Ref-1] was used to evaluate patients’ responses to treatment. RECIST response categories include complete response (CR), partial response (PR), stable disease (SD) and progressive disease (PD). In addition to these four primary ratings, a patient’s response to treatment is classified as unevaluable (abbreviated NE) when no imaging/measurement is performed at a particular time point.

3.1. Blinded Treatment Phase Subjects who qualify for enrollment into the phase-2 portion of the study will be randomized in a 1:1 ratio to receive study treatment of EP with placebo or EP with tarextumab. The randomization will be balanced on the choice of platinum therapy (cisplatin versus carboplatin) and the prior use of whole brain radiation (WBR) or prophylactic cranial irradiation (PCI). Changing the choice of platinum therapy is not permitted once the subject is randomized. Treatment for each subject will begin on Cycle1, Day 1 (the first dosing day). Etoposide 100 mg/m2 will be given on Days 1, 2 and 3 and cisplatin 75 mg/m2 or carboplatin to an AUC of 5 mg/mL/min will be given on Day 1 of every 21-day cycle for 6 cycles. Subjects may remain in the blinded treatment phase to continue one of the chemotherapy drugs if the other is held or discontinued prior to completing 6 cycles of EP and prior to disease progression. For subjects who have study drug held or discontinued for tolerability reasons, EP chemotherapy should continue to the completion of 6 cycles. Subjects may continue study drug if one or both of the chemotherapy drugs is held or discontinued prior to completing 6 cycles of EP and prior to disease progression.

After the completion of 6 cycles of EP, subjects who do not have disease progression and have not had WBR or PCI prior to study entry and are good candidates for PCI according to the


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investigator should receive PCI within 8 weeks after the last dose of chemotherapy at a total dose of 25 Gy in 10 fractions. If subjects discontinue EP with treatment-related toxicities prior to completing 6 cycles and are good candidates for PCI per the investigator, PCI can be initiated at any time determined appropriate by the investigator. Subjects who do not receive PCI within 8 weeks after the last dose of chemotherapy can have PCI later during the study as determined by the investigator. Study drug (tarextumab or placebo) administration should continue at every 21-day cycle between the completion of chemotherapy and the initiation of PCI. PCI should not be initiated within 2 weeks of study drug administration and study drug will be held during the PCI treatment period. Subjects will resume study drug alone ≥14 days after completion of PCI, until disease progression or unacceptable treatment-related toxicities or withdrawal of consent. Subjects will discontinue study treatment if there is evidence of central nervous system (CNS) metastasis.

3.2. Follow-Up Subjects who discontinue study treatment for any reason other than disease progression will be followed with tumor assessment every 6 weeks (42 ±5 days) during follow-up until documented disease progression or initiation of new anti-cancer therapy, whichever is sooner. Additionally, subjects who are discontinued from study treatment will be followed for survival and any subsequent anti-cancer therapies. Survival follow-up information and subsequent anti-cancer therapies, including systemic therapies, surgery (resection of metastatic disease), and radiation therapy will be collected during telephone calls, through subjects medical records, and/or clinic visits every 3 months starting from the last study treatment until death, loss to follow-up, or study termination by the sponsor. The study staff may use a public information source (e.g., county records) to obtain information about survival status only.

4. DETERMINATION OF SAMPLE SIZE The following assumptions and methods for determining the sample size for the study were copied from the study protocol. Since this SAP only covers analyses planned for the phase-2 portion of the study, details on the determination of sample size for the phase-1b portion of the study have been omitted intentionally.

At the final analysis we will evaluate the effect of tarextumab on PFS in subjects in the intention to treat (ITT) population (defined in section 6.1). The final analysis will take place when 91 progression events have been observed or 10 months after the completion of enrollment whichever occurs first.

Denote the treatment effect in terms of the log of the hazard ratio (HR) by . The null hypotheses for testing homogeneity of PFS distributions across treatment arms is:

And the alternative hypothesis is:

The power and type-1 error rate for the log rank test of this hypothesis is presented in Table 1.


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Table 1. Progression-Free Survival: Power for the Alternative Hypothesis

Analysis 1 Analysis 2 Final Analysis Total Number of Events 61 76 91 Z-Statistic (reject the null) [1] 3.168 2.301 1.036 P-value (1 sided) 0.00077 0.011 0.15 Z statistic (reject the Alt) [2] -1.773 -1.486 -1.079 P-value (1 sided) 0.038 0.0690 0.1400 Cumulative Type 1 Error (1-sided) 8e-04 0.0107 0.1501 Cumulative Power HR=0.75 0.0204 0.1479 0.6318 HR=0.67 0.0543 0.2897 0.8090 HR=0.65 0.0687 0.3365 0.8460 HR=0.60 0.1204 0.4709 0.9194 HR=0.50 0.3223 0.7647 0.9884 Cumulative Probability of Stopping for Harm Alternative 4e-04 8e-04 0.0018 Null 0.0381 0.0762 0.1501 HR=1.33 (1/0.75) 0.2580 0.4246 0.6275 HR=1.49 (1/0.67) 0.4172 0.6170 0.8052 HR=2.00 (1/0.50) 0.8248 0.9412 0.9877 [1] The boundary for rejecting the null hypothesis for efficacy is obtained from the gamma(-16) alpha spending function. [2] The boundary for rejecting the null hypothesis for harm is obtained from the gamma(-4) alpha spending function.

With 91 events at the final analysis, there is 80% power with 0.15 type 1 error to detect an HR of 0.67. There is a 7.6% chance of stopping early for harm under the null hypothesis; a 42.5% chance of stopping early for harm if the HR=1.33 (1/0.75); a 61.7% chance of stopping early for harm if the HR=1.49 (1/0.67); and a 94.1% chance of stopping early for harm if the HR=2.00 (1/0.5).

Analyses 1 and 2 will take place at the last two quarterly safety review meeting of the Data Safety Monitoring Board (DSMB). The estimated numbers of events at these times are presented in Table 1. If the number of events differs from what is presented, then the efficacy and safety boundaries will be recalculated using the spending functions which are footnoted in Table 1.

Overall survival is a secondary endpoint in this study. An analysis of OS will take place at the time of each analysis for PFS as well as at the time that the final analysis of PFS takes place. The final analysis of OS will take place when there are 98 events or 6 months after the final analysis for PFS, whichever occurs first. Table 2 and Figure 1 present enrollment, PFS events and Deaths over time assuming a control hazard of progression beyond 9 months of 0.1386.

Table 2. Enrollment, Progressions and Deaths over Time – Control Hazard of Progression of 0.1386 Beyond 9 Months Study Time (months) 6 12 13 14 15 16 17 18 19 20 Cumulative Enrolment 22 77 85 89 91 105 119 133 134 134 Total PFS Events 5 31 38 43 49 55 62 69 75 80 Total PFS Events-2 [1] 6 35 42 48 54 61 68 76 82 87 Total Deaths 3 19 23 27 32 37 42 49 55 61 Total Deaths-2 [1] 4 22 27 32 37 42 49 56 63 69 Censored PFS (tarextumab) 1 5 6 7 8 9 10 11 12 13 Censored PFS (placebo) 1 4 5 6 7 8 9 9 10 11


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Study Time (months) 21 22 23 24 25 26 27 28 29 30 Cumulative Enrolment 134 134 134 134 134 134 134 134 134 134 Total PFS Events 85 90 94 96 97 98 99 99 100 100 Total PFS Events-2 [1] 92 98 101 103 104 104 105 105 105 106 Total Deaths 66 72 77 81 86 91 95 99 102 105 Total Deaths-2 [1] 75 81 86 91 96 100 104 108 111 114 Censored PFS (tarextumab) 14 15 15 16 16 16 16 16 16 17 Censored PFS (placebo) 12 12 13 13 13 13 13 13 13 13 [1] Total PFS Events-2 and Total Deaths-2 refer, respectively, to the expected numbers of progressions and deaths when tarextumab does not prolong progression or death.

Figure 1. Enrollment, Progressions and Deaths over Time – Control Hazard of Progression of 0.1386 Beyond 9 months

Calculations in Table 2 and Figure 1 take into account non constant hazards for PFS and OS described in Table 3 and Table 4, respectively. Estimates of non constant hazard are from Kaplan-Meier (KM) curves for PFS and Survival in Noda et al [Ref-2] and Hanna et al [Ref-3]. Regarding enrollment it was initially assumed that there is a ramp up time of 5 months with a starting enrollment of 4 subjects per months and that the maximum enrollment rate is 6 subjects per month. The enrollment in Table 10 and Figure 1 represents the observed enrollment up to January 2016 and the remaining enrollment is assumed to be 15 subjects per month.

The censoring rate was initially assumed to be 40% of the rate at which events occur in the control arm and 60% of the rate at which events occur in the tarextumab arm. When 79 PFS events accrued in the study, there were 39 censored observations for a censoring rate of 39/(39+79)=33%. This information was used to recalibrate the total number of events at the final analysis, the type 1 error rate and power.


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Table 3. Hazards for Piece-Wise Exponential Model of Progression Free Survival Period 0-5 months 5-7 months 7-8 months >8 months

% Change in Proportion without an event (Change in PFS)

0.50 (1.00 to 0.50)

0.50 (0.50 to 0.25)

0.50 (0.25 to 0.125)

0.50 (0.125 to 0.0625) 8-18 months [1] 8-11 months [2]

Hazard Control 0.1386 0.3466 0.6931 0.0693, 0.2310 Hazard Treatment 0.0901 0.2253 0.4505 0.0451, 0.1502 Hazard Ratio 0.65 0.65 0.65 0.65 [1] Noda et al [Ref-2] [2] Hanna et al [Ref-3]

Table 4. Hazards for Piece-Wise Exponential Model of Overall Survival Period 0-5 months 5-7 months 7-8 months >8 months

% Change in Proportion without an event

0.50 (1.00 to 0.50)

0.50 (0.50 to 0.25)

0.60 (0.25 to 0.10)

0.467 (0.15 to 0.08)

18-24 months [1] Hazard Control 0.07702 0.1155 0.1703 0.127 Hazard Treatment 0.05006 0.07509 0.1107 0.0825 Hazard Ratio 0.65 0.65 0.65 0.65 [1] Hanna et al [Ref-3]

We see from Table 2 that approximately 70% of the 98 deaths required for the final analysis of survival are expected to be observed at the time of the final analysis for PFS. Table 5 presents the power to detect benefit in OS for several HRs assuming that type 1 error is controlled at the 0.15 level and additional analyses take place at approximately 50%, 67% and 83% of full information. These additional analyses will take place at the quarterly DSMB review meetings. If the actual number of events at the review meetings differs from what is presented in the table, the efficacy and safety boundaries will be recalculated using the spending functions footnoted in Table 5.

Table 5. Overall Survival: Power for the Alternative Hypothesis

Analysis 1 Analysis 2 Analysis 3 Final Analysis Total Number of Events 49 66 81 98 Z-Statistic (reject the null) [1] 3.889 3.174 2.333 1.036 P-value (1 sided) 0.000050 0.00075 0.0098 0.15 Z statistic (reject the Alt) [2] -2.1 -1.848 -1.511 -1.082 P-value (1 sided) 0.018 0.032 0.0658 0.139 Cumulative Type 1 Error (1-sided) 1e-04 8e-04 0.0099 0.1501 Cumulative Power HR=0.75 0.0020 0.0226 0.1499 0.6511 HR=0.682 0.0054 0.0530 0.2711 0.8047 HR=0.65 0.0086 0.0777 0.3471 0.8637 HR=0.60 0.0178 0.1365 0. 4869 0.9324 HR=0.50 0.0717 0. 3610 0. 7846 0. 9918 Cumulative Probability of Stopping for Harm Alternative 3e-04 5e-04 9e-04 0.0019 Null 0.0179 0.0381 0.0744 0.1501 HR=1.33 (1/0.75) 0.1372 0.2660 0.4332 0.6470


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Analysis 1 Analysis 2 Analysis 3 Final Analysis HR=1.47 (1/0.682) 0.2235 0.4037 0.6007 0.8000 HR=2.00 (1/0.50) 0.6278 0.8426 0.9496 0.9911 [1] The boundary for rejecting the null hypothesis for efficacy is obtained from the gamma(-16) alpha spending function. [2] The boundary for rejecting the null hypothesis for harm is obtained from the gamma(-4) alpha spending function.

With 98 deaths at the final analysis, there is 80% power with 0.15 type 1 error to detect a HR of 0.682. There is a 7.4% chance of stopping early for harm under the null hypothesis, a 43.3% chance of stopping early for harm if the HR=1.33 (1/0.75); a 60.1% chance of stopping early for harm if the HR=1.47 (1/0.682); and a 95.0% chance of stopping early for harm if the HR=2.00 (1/0.5).

5. GENERAL ANALYSIS CONSIDERATIONS The statistical analyses will be reported using summary tables, figures and listings (TFLs). Unless otherwise noted, all statistical testing will be two-sided and will be performed at the 0.05 level of significance.

Continuous variables will be summarized with the number of non-missing values, estimated means, standard deviations, medians, 25th and 75th percentiles, and observed minimum and maximum values.

Categorical variables will be summarized by counts and by percentages. The percentage of patients within a category will be displayed in parentheses rounded to the nearest tenth of one percent. However, when the number of patients within a category is 0, then the percentage (i.e., 0.0%) will be omitted.

Time-to-event variables will be summarized by KM estimates of quartiles, observed minimum and maximum values, and the number of censored observations. The hazard will be estimated by the sum of all individual follow-up times in days divided by 365.25.

Any durations of time expressed in months will be reported in proportional “months” according to the formula

months days.

Summary tables will be presented by treatment group. Individual subject data will be presented in data listings.

The analyses described in this plan are considered a priori, in that they have been defined prior to database lock and prior to breaking the treatment blind. If any a posteriori analyses (i.e., analyses not included in this SAP) are performed, they will be identified as such in the CSR where the objective and rationale for executing any a posteriori analyses will be documented.

5.1. Analysis Software In general, data analyses and tabulations will be executed using SAS® version 9.2 or higher. SAS® programing statements will be validated by an independent programmer and SAS® output will undergo a senior-level statistical review to confirm that that all data manipulations and calculations are accurate and statistically valid methods have been implemented. Checks will be made to ensure accuracy and consistency with this plan and within and between TFLs. Upon


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completion of validation and quality-review procedures, all documentation will be collected and filed by the project statistician or designee.

5.2. Baseline Values Unless otherwise noted, baseline is defined as the last non-missing value recorded prior to the first dose of study drug. Therefore, data collected during any unscheduled visits will be used in the determination of baseline values, as applicable.

5.3. Missing Values No imputations will be made for missing values. Summaries will be based on observed data only.

5.4. Subgroup Analyses Plans for analyses of subgroups based on the presence or absence of anti-tarextumab antibodies are presented in section 11.7 below.

No analyses by baseline characteristics or study center are planned.

Subgroup analyses by baseline Notch3, Hes1, Hey2, Hey1 and Hes6 expression levels are not planned, but the impact these potentially important covariates have on the efficacy of tarextumab will be assessed through statistical modeling (see sections 8.1, 8.3, 8.6 and 8.7).

5.5. Multiple Comparisons/Multiplicity A gamma(-12) spending function will be used to control the type-1 error for the assessment of efficacy and a gamma(-4) spending function will be used to control the type-1 error for harm arising from multiple analyses of PFS (see Table 1). The same spending functions will be used to control for multiplicity when testing OS (see Table 5).

6. ANALYSIS DATA SETS The analysis set for the phase-2 portion of the study will include data from all subjects who were randomized in the phase-2 portion to receive either tarextumab or control. Data from subjects who were enrolled in the phase-1b portion of the study will be excluded from the analysis set.

The planned data cut for the formal final analysis of PFS will take place at the point where 91 PD events have occurred or 10 months after the completion of enrollment, whichever occurs first. However, the actual data cut for the final formal analysis of PFS may be extended beyond 10 months after the completion of enrollment for reasons concerning study conduct (e.g., if patients are randomized but not treated). This will ensure that the study will have 81% power to detect an HR of 0.67 (improvement in median PFS from 4.8 months to 7.2 months) with an associated total one sided type-1 error rate of 0.15 (see section 4).

When the data cut for the formal analysis of PFS is taken, the following rules will be applied to determine which data are included in statistical analyses and data summaries. The goal of these data filtering rules is to ensure that that only certain data records occurring after the cutoff date 01-DEC-2016 are included.

1. No filter will be applied to the Death Report CRF or Follow Up After Discontinuation of Study Treatment CRF.


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2. On CRF pages with a start/stop date (such as AE and CM), the data will be kept if either the start or stop date is on or prior to the cut off date. Note: if the start date is on or prior to the cut off, the record will be retained, therefore there may be stop dates that appear in listings that are post the cut off date.

3. If the outcome for an AE is death, the record will be retained even if the death occurred after the cut off date. Note: the record will be kept only for the purpose of preserving the death date (for efficacy analysis). The AE however will not be used in summaries of AEs.

4. In the event a partial date is reported and there is a chance the event/occurrence could be on or prior to the cutoff date, then that record will be kept for analyses and summaries. For instance, a record with a partial date of “2016” would be kept for analysis. Likewise, a record of “DEC-2016” would also be kept since the actual event date could have been 01DEC2016.

An additional data filtering rule specific to analyses of PFS and DOR is that deaths reported on the Death Report CRF and AE CRF where death is reported after the cut off date will not be considered.

Additional data filtering rules specific to analyses of OS are:

1. Death reported on Death Report CRF and AE CRF (end date of AE), regardless of date will be included in OS analyses. That is deaths reported after the cutoff date will not be filtered.

2. If the date of death reported on the Death Report CRF and an AE CRF is not the same, the date of death reported on the Death Report CRF will be used. SynteractHCR will notify the sponsor of the discrepancy.

3. The Follow-Up Discontinuation CRF does not explicitly collect date of death. The form only collects the Date of Survival Assessment and Last Known Survival Date. If a patient’s death is reported only on the Follow-Up Discontinuation CRF, then SynteractHCR will notify the sponsor, and the sponsor will advise SynteractHCR how to proceed.

Upon request, a listing of death dates can be generated to show which patients have died and which CRF page was used to acquire the death date.

The planned data cut for the final analysis of OS will be 6 months after the data cut for PFS or when 98 deaths have been observed, whichever occurs first. Once again, the actual data cut for the final formal analysis of OS may be extended beyond 6 months after the PFS data cut for reasons concerning study conduct.

6.1. Analysis Populations The following five groups of study patients will be used for statistical analyses.

1. The ITT patient population includes all patients randomized to receive study drug regardless of whether they actually received study drug and regardless of whether evidence is found indicating they failed to meet study inclusion/exclusion criteria or had other protocol violations. When the ITT patient population is analyzed, patients are grouped according to


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their randomized treatment regardless of actual treatment received. The ITT patient population is the analysis population for demographics and baseline characteristics and for all statistical inference and primary tests of hypotheses related to efficacy endpoints.

2. The safety patient population is the subset of ITT patients who received at least one dose of study drug. When the safety patient population is analyzed, patients are grouped according to actual treatment received. Tarextumab is considered a patient’s “treatment received” in the safety patient population if the patient received at least one dose of tarextumab (complete or incomplete dose) any time during the study. The safety patient population is the analysis population for all analyses of safety data.

3. The per-protocol (PP) patient population is the subset of safety patients who either (a) have at least one response evaluation on study, or (b) die prior to their first scheduled response evaluation. When the per-protocol patient population is analyzed, patients are grouped according to actual treatment received. The per-protocol population is used for sensitivity (secondary, supportive) analyses of efficacy endpoints.

4. The pharmacokinetic (PK) patient population is comprised of all subjects who received at least one complete dose of tarextumab and have at least one post-dose PK sample.

5. The immunogenicity patient population is comprised of all subjects who had a baseline and one or more follow-up samples obtained for quantifying anti-tarextumab antibody.

7. SUMMARIES OF PATIENT CHARACTERISTICS

7.1. Subject Disposition Subject disposition information will be summarized for all subjects by treatment arm. Summaries will include the number of subjects randomized, the number of subjects in each analysis population, the primary reason for stopping each study drug (randomized treatment [tarextumab or placebo], selected platinum therapy [cisplatin or carboplatin] and etoposide), and the primary reason for withdrawing from the study.

The physician’s choice of platinum therapy (cisplatin or carboplatin) was used as a stratification variable by the dynamic randomization system. The actual platinum received (as documented on earliest Platinum Therapy Infusion CRF [e.g., Cycle 1, Day 1]) will be summarized in a 2x2 frequency table against the platinum-therapy strata under which a patient was randomized.

7.2. Protocol Deviations Protocol deviations will be collected and provided by the sponsor. Major protocol deviations that could potentially affect the integrity of efficacy/safety analysis results will be identified prior to database lock and categorized. Major protocol deviations categories may include, but are not limited to enrollment violations, dosing violations, prohibited concomitant therapy violations, and continuation of therapy when treatment should have been discontinued. Major protocol deviations will be summarized by deviation category and treatment group.

7.3. Demographics and Baseline Characteristics Demographic variables include age, sex, child-bearing potential for females, ethnicity and race. Age will be calculated in years relative to the informed consent date. Baseline characteristics include height, weight, body mass index (BMI), smoking history and Eastern Cooperative


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Oncology Group (ECOG) performance status. Descriptive statistics will be presented for age, height and weight; and frequency counts and percentages will be presented for sex, child-bearing potential, ethnicity, race, smoking history (never smoked, ex-smoker, or current smoker) and ECOG performance status. Demographic and baseline characteristics will be summarized for the ITT, safety, PP and immunogenicity populations.

ES-SCLC history, including time since ES-SCLC diagnosis, histological/cytological type (small cell only, mixed type, or other), anatomical location of primary tumor, and number of disease sites (1, 2 or ≥3) at study entry will be summarized by treatment group for the ITT and safety populations. The time from ES-SCLC diagnosis to randomization will be quantified in months according to the formula shown in section 5. Summary statistics for baseline values of total tumor length (abbreviated SLD for sum of longest diameters) will be included in the analyses of efficacy endpoints.

Baseline levels of Notch3, Hes1, Hey2, Hey1 and Hes6 will be summarized as a continuous variable in the ITT, safety and per-protocol populations.

Prior therapies (surgeries and radiotherapies) for ES-SCLC will be summarized for the ITT and safety populations.

Patients’ medical and surgical histories will be displayed in a data listing.

8. EFFICACY ENDPOINTS Primary analyses of efficacy endpoints will use data from the ITT population. Additional efficacy analyses will be performed using data from only the PP population, but these analyses are considered secondary.

Efficacy endpoints include investigator-assessed PFS, assessment of SLD as a continuous variable, ORR defined as the proportion of patients achieving a CR or PR, duration of response (DOR), sites of progression, OS and landmark survival at 180, 360, 540 and 720 days.

As mentioned in section 5 above,

Continuous variables will be summarized with the number of non-missing values, estimated means, standard deviations, medians, 25th and 75th percentiles, and observed minimum and maximum values.

Categorical variables will be summarized by counts and by percentages. The percentage of patients within a category will be displayed in parentheses rounded to the nearest tenth of one percent. However, when the number of patients within a category is 0, then the percentage (i.e., 0.0%) will be omitted.

Time-to-event variables will be summarized by KM estimates of quartiles, observed minimum and maximum values, and the number of censored observations. The hazard will be estimated by the sum of all individual follow-up times in days divided by 365.25.

8.1. Progression-Free Survival On study tumor assessments are those that meet the following criteria:


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1. No gap of >91 days between successive tumor assessments among those on or prior to the on study tumor assessment. (Note: a tumor assessment for which “Not Evaluated” is entered into the database does not qualify as a tumor assessment.)

2. No prior initiation of non-protocol anticancer therapy.

PFS, the primary endpoint of the study, is defined as the time from randomization (Day 1) until the first occurrence of death or disease progression based on investigator assessments of tumor response per the RECIST criteria. Progressions that are not determined from on study tumor assessments as well as deaths occurring more than 49 days from the last on-study tumor assessment are not treated as progression events. Subjects without a progression event will be censored at their last on study tumor assessment.

In addition two special cases will be handled in a manner consistent with the above rules as follows:

1. Patients whose first tumor assessment is >91 days from randomization will be censored on the date of randomization with a PFS of 1 day.

2. Patients who never had an on study tumor assessment and who did not die within 49 days (the scheduled time between tumor assessments plus 7 days) after randomization will be censored on the date of randomization with a PFS of 1 day.

The KM method will be used to estimate the proportions of subjects over time without progression or death and the median progression-free survival time. KM curves will be plotted by treatment group. The 95% confidence intervals for median progression-free survival time will also be calculated for each treatment arm. The p-value for treatment effect will be generated using a stratified log rank test using platinum choice (cisplatin or carboplatin; see page 6) and prior treatment modality (WBRT or PCI) as stratification factors. The HR and its 95% confidence interval will be estimated using a Cox proportional hazards (PH) model with main effects for treatment and the aforementioned stratification factors.

According to the study design, administrations of randomized treatment (tarextumab or placebo only; without EP) may continue in 21-day cycles from the completion of 6 cycles of EP until the initiation of PCI. The following analysis of PFS will be conducted in order to determine if there is a treatment benefit when tarextumab is administered in combination with EP. Subjects who have not progressed will have their PFS censored 35 days (the scheduled time for 1 treatment cycle plus 7 days) following the last dose of Carboplatin/Cisplatin or EP. KM and Cox PH analyses will be the same as those described above.

The impact of the biomarkers Notch3, Hes1, Hey2, Hey1 and Hes6 on PFS will be evaluated with a Cox PH model with treatment, biomarker and treatment-by-biomarker interaction included in the model as independent variables. A separate Cox PH model will be used for each biomarker.

Sensitivity analyses for PFS include replicating the primary log-rank analysis using the PP population and unstratified log-rank tests using the ITT and PP populations.

The planned timing for the primary analysis of PFS is stated in section 5.5 above.


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8.2. Total Tumor Length Total tumor length is the sum of the longest diameters (SLD) for the target lesions as defined by RECIST criteria. Standard summary statistics for a continuous variable (identified in section 5) will be computed for SLD at baseline and the Cycle-3, Day-1 (C3D1) and Cycle-5, Day-1 (C5D1) assessments. Summary statistics will also be presented for changes from baseline at the C3D1 and C5D1 tumor assessments. Ninety-five percent confidence intervals for the mean SLD at each time point will also be computed. Two analysis of covariance (ANCOVA) models for SLD will be used to test the hypothesis that there is no difference between treatment arms with regard to changes in tumor length from baseline at the C3D1 assessment.

The difference between the follow-up and baseline SLD (e.g., SLDC3D1 – SLDbaseline) will be the dependent variable in the first ANCOVA model. Treatment, platinum choice (cisplatin versus carboplatin) and prior treatment modality (WBRT or PCI) will be categorical factors in the model, and SLDbaseline will be included as a continuous covariate.

The log of the ratio of follow-up to baseline SLD (e.g., log [SLDC3D1/SLDbaseline]) is the dependent variable in the ANCOVA model. Treatment, platinum choice and prior treatment modality will be categorical factors in the model, and log SLDbaseline will be included as a continuous covariate.

Missing values will not be imputed.

Separate but similar analyses will be performed for changes in tumor length from baseline at the C5D1 assessment.

A waterfall plot of best percent change in SLD across all tumor assessments relative to baseline will be presented.

Rates of change in SLD from baseline to C3D1, C5D1 and at progression will be evaluated.

The rate of change in SLD at CxD1 is defined as

where d2 is the number of days between the baseline assessment (Day 1) and the CxD1 assessment.

Rate of change in SLD at CxD1 will be missing for subjects who did not have a RECIST assessment corresponding to the CxD1 visit.

The rate of change in SLD from its on-study nadir to progression is defined as

where d1 is the number of days between the on-study SLD nadir and progression.

Rate of change in SLD at progression will be missing for subjects who did not have a RECIST assessment of PD on study and for subjects whose on-study SLDnadir = 0.


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Comparisons of these rates of change between the two treatment arms will be made using an analysis of variance (ANOVA) model with treatment, platinum choice (cisplatin versus carboplatin) and prior treatment modality (WBRT or PCI) as categorical independent variables.

8.3. Overall Response Rate A patient’s best overall response is defined as the best investigator-assessed RECIST response to treatment category recorded since the start of the treatment. The hierarchy of response ratings, best to worst, is CR, PR, SD, PD, followed by NE. The numbers and percentages of subjects achieving each of these response categories will be summarized within treatment group.

The ORR, defined as the proportion of patients achieving a CR or PR, and its 95% confidence interval will be computed within treatment group. The p-value for equality between treatment groups will be calculated for the two groups using a logistic regression model including treatment, platinum choice (cisplatin versus carboplatin) and prior treatment modality (WBRT or PCI) as categorical independent variables. Patients without any post-baseline tumor assessments will be classified among those never achieving a CR or PR.

The impact of the biomarkers Notch3, Hes1, Hey2, Hey1 and Hes6 on ORR will be evaluated with a logistic regression model with treatment, biomarker and treatment-by-biomarker interaction included in the model as independent variables. A separate logistic regression model will be used for each biomarker.

8.4. Duration of Response Analyses of DOR include only patients who achieved a CR or PR; patients failing to achieve a CR or PR during the study are omitted from analyses of DOR. If the number of patients achieving a CR or PR is not sufficient to produce meaningful KM curves, then the planned analyses for DOR may be abandoned.

DOR is defined as the number of days from the first CR or PR until the first occurrence of death or disease progression based on investigator assessments of tumor response per the RECIST criteria. Progressions that are not determined from on study tumor assessments as well as deaths occurring more than 49 days from the last on-study tumor assessment are not treated as progression events. Subjects achieving a CR/PR but without a subsequent progression event will be censored at their last on study tumor assessment.

In addition two special cases will be handled in a manner consistent with the above rules as follows:

1. Patients whose next tumor assessment (following the first CR/PR) is >91 days after the first CR/PR will be censored on the date of the first CR/PR with a DOR of 1 day.

2. Patients who never had an on study tumor assessment after the first CR/PR and who did not die within 49 days (the scheduled time between tumor assessments plus 7 days) after the first CR/PR will be censored on the date of first CR/PR with a DOR of 1 day.

The KM method will be used to estimate the proportions of CR/PR patients over time who have not experienced RECIST disease progression and the median DOR. KM curves will be plotted and 95% confidence intervals for median DOR will also be calculated for each treatment arm. The HR, its 95% confidence interval and the p-value for testing the statistical significance of the


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treatment effect will be generated using a Cox PH model with main effects for treatment, platinum choice (cisplatin versus carboplatin) and prior treatment modality (WBRT or PCI).

8.5. Sites of Progression Sites of progression will be categorized as stemming from (1) a new lesion or (2) progression of an existing lesion. Treatment-group distributions based on this binomial categorization will be tested using a chi-square test. Then “new lesions” will be further categorized by anatomical site. Patients with new lesions at multiple anatomical locations will be classified as a single category. The resulting multinomial distributions will also be compared across treatment groups using a chi-square test.

8.6. Overall Survival OS is defined as the number of days from randomization (Day 1) until death. The following rules will be used to define censored observations and censoring times for OS.

1. A patient for whom no death date is reported will have OS censored on the last contact date (defined on page 6). When evaluating the last contact date using the ‘Follow-Up After Discontinuation of Study Treatment’ CRF, both of the ‘date of survival assessment’ (if checked ‘alive’ for ‘subject status’) and the ‘last known survival date’ (if checked ‘alive or ‘lost to follow-up’ for ‘subject status) will be considered.

2. Patients lacking data after randomization who do not die have their event time censored on the date of randomization with duration of 1 day.

3. All patients alive on the date of the 98th sequential patient death will have their OS censored on the day following the date on which the 98th patient died. All patient deaths will be counted towards the total of 98, independent of which treatment arm the deceased patients were randomized to.

The KM method will be used to estimate survival proportions over time. KM survival curves will be plotted and 95% confidence intervals for median OS will also be calculated for each treatment arm. The HR, its 95% confidence interval and the p-value for testing the statistical significance of the treatment effect will be generated using a Cox PH model with main effects for treatment, platinum choice (cisplatin versus carboplatin) and prior treatment modality (WBRT or PCI).

OS will also be analyzed separately for two subsets of ITT patients defined by platinum choice (cisplatin or carboplatin). In this case, the p-value for testing the statistical significance of the treatment effect will be generated using a Cox PH model with main effects for treatment and prior treatment modality only.

The impact of the biomarkers Notch3, Hes1, Hey2, Hey1 and Hes6 on OS will be evaluated with a Cox PH model with treatment, biomarker and treatment-by-biomarker interaction included in the model as independent variables. A separate Cox PH model will be used for each biomarker.

The planned timing for the primary analysis of OS is stated in section 5.5 above.

8.7. Landmark Survival KM estimates of OS at 180, 360, 540 and 720 days will be summarized. Comparisons between the two treatment groups will be made using independent Z tests.


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9. EXPLORATORY ANALYSES An exploratory analysis was undertaken by the sponsor using blinded data to examine the relationship between PFS and the Notch pathway markers HES1, HES6 and NOTCH3. The biomarker values were normalized so that the distributions had mean 0 and variance 1, then a Cox PH model was fit using the three main effects, the three two-way interactions, and the three-way interaction as independent variables. Estimated coefficients are show in Table 6.

Table 6. Cox PH Model between Progression-Free Survival and Three Biomarkers

Independent Variable Estimated Coefficient

Exponentiated Coefficient

Standard Error Z-Score P-Value

HES6 0.17396 1.190 0.192 0.9059 0.3700 HES1 0.00154 1.002 0.134 0.0115 0.9900 NOTCH3 0.01248 1.013 0.189 0.0660 0.9500 HES6*HES1 0.68087 1.976 0.241 2.8300 0.0047 HES6*NOTCH3 –0.56935 0.566 0.247 –2.3021 0.0210 HES1*NOTCH3 0.15654 1.169 0.191 0.8215 0.4100 HES6* HES1*NOTCH3 1.07604 2.933 0.357 3.0175 0.0025 Model notes: n=89 (56 observations deleted due to missing values); number of events=58; Likelihood ratio test=16.3 (7 degrees of freedom); p=0.0222

Judging statistical significance at the two-sided 0.05 level, the two statistically significant terms which included NOTCH3 were used to establish a NOTCH-3-ralated PFS index (N3RPI).

Patients were then split into two groups (High N3RPI or Low N3RPI) based on whether their score was above or below the median N3RPI (0.066), respectively. A patient whose N3RPI was equal to the median was placed into the Low N3RPI group. Patients in each of these two groups were then split into two additional groups (High NOTCH3 or Low NOTCH3) based on whether their score was above or below the overall median NOTCH3 value (–0.046), respectively. A patient whose NOTCH3 was equal to the median was placed into the Low NOTCH3 group.

The KM curves for PFS and for OS in these four subgroups are presented in Figure 2 and Figure 3, respectively. For patients with an N3RPI above the median N3RPI (i.e., High N3RPI), the difference in PFS between the High and Low NOTCH3 groups is associated with a p-value of 0.09.


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Figure 2. Progression-Free Survival Kaplan-Meier Curves for Patients with High and Low N3RPI


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Figure 3. Overall Survival Kaplan-Meier Curves for Patients with High and Low N3RPI

It is noteworthy that high NOTCH3 is trending to be beneficial for patients with low N3RPI, whereas high NOTCH3 appears to be detrimental when N3RPI is high. This prompted the exploratory hypothesis that NOTCH 3 inhibition with tarextumab will improve PFS and OS in patients who have high N3RPI. In the case where N3RPI is high, tarextumab may be able to reduce the detrimental effects associated with high Notch 3 expression.

The following exploratory analyses will be carried out to test this hypothesis. The analysis population (ITT or per-protocol) will be divided into two N3RPI groups: High N3RPI and Low N3RPI (as defined above). Independent Cox PH models will be fit to data from each of the two groups. The models will include effects for treatment (tarextumab or placebo), NOTCH3 value, and the interaction between treatment and NOTCH3. The treatment HR and a 95% CI for the HR will be estimated at the quartiles of the NOTCH3 distribution. The same analysis will be carried out for “high” and “low” patient subgroups based on each of the biomarkers (Hes1, Hes6, Hey1 and Hey2).

10. PHARMACOKINETIC ENDPOINTS Investigating the PK of tarextumab in combination with EP is an objective of this study, but a detailed analysis plan is outside the scope of this document. Therefore, no PK analyses are discussed here.


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11. SAFETY ENDPOINTS Analyses of safety endpoints will use data from the safety population. Safety endpoints listed in the study protocol include adverse events (AEs), serious adverse events (SAEs), clinical laboratory parameters, and results from testing for anti-tarextumab antibodies. Other safety endpoints include vital signs and electrocardiogram (ECG) results.

11.1. Treatment Cycles and Dosing Dosing with tarextumab (or placebo), etoposide and EP will be summarized by the number of cycles of treatment administered (duration of treatment), the number of doses of each study medication, and the extent of exposure to each study medication. Placebo exposure will be summarized in tarextumab-equivalent units, that is, by the number of milligrams of tarextumab the placebo “replaced” during treatment-blinded dosing.

Body surface area (BSA) is determined for each visit. The latest assessment of BSA on or before each visit will be used to determine the protocol-specified amount of drug (mg) in a dose.

11.1.1. Dose Intensity Dose intensity is defined as the total dose a patient actually received divided by the total dose the patient should have received had there been no missed doses, dosing delays or dosage reductions.

Dose intensityTotal amount of drug received (mg)

protocol-specified, planned amount of drug (mg)

The actual amount of drug received is obtained from the dosing records.

The protocol specified amount of drug to be received for each treatment is provided below.

Etoposide The number of doses of Etoposide that should be administered per protocol is

321 21 21Etop

Stop Start Stop Start Stop Startfloor h floor ,

where

1 if 21 x 0( ) 2 if 21 x 1

3 if 21 x 2Etoph x

Start is the date of the first dose of treatment. Stop is the last dose of treatment.

The amount of drug contained in a dose of Etoposide is 2100 / BSAmg m

Carboplatin/Cisplatin/Study Drug The number of doses of Carboplatin, Cisplatin or Study Drug that should be administered per protocol is


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121 21 21

Stop Start Stop Start Stop Startfloor h floor ,

where

( ) 1 if 21 x 0h x

Start is the date of the first dose of treatment and Stop is the last dose of treatment for the respective drugs. Treatment period is (last treatment date – first treatment date + 2), allowing 2 extra days to cover any following early visits.

The mg amount of drug contained in a dose of Carboplatin is

AUC of 5 ( 25)GFR

The mg amount of drug contained in a dose of Cisplatin is 280 /mg m BSA

The amount of drug contained in a dose of study drug is

15 / weightmg kg

Weight, BSA and GFR are to be determined at each visit. Use the latest weight, BSA and/or GFR on or before each dose to determine the amount of drug (mg) in a dose.

11.1.2. Dosing Compliance Dosing compliance is defined as the ratio of the number of doses administered to the number of doses planned according to the schedule outlined in the study protocol.

Dosing compliance

where Nplanned is the number of doses planned according to the schedule outlined in the study protocol and Nadministered is the number of doses the patient received.

Dosing compliance will be summarized as a continuous variable (see Section 5) and by the numbers of patients with 0% to <20%; 20% to <40%; 40% to <60%; 60% to <80%; 80% to <100%; and 100% compliance. The reasons for delaying and/or withholding doses randomized study drug, selected platinum agent and etoposide will also be summarized.

11.2. Adverse Events Reported AE terms will be mapped to preferred terminology using Medical Dictionary for Regulatory Activities (MedDRA) version 17.1. All reported events will appear in AE listings, however only treatment-emergent adverse events will be summarized. A treatment-emergent adverse event (TEAE) is an AE that starts or increases in severity any time after the first administration of any randomized study drug (i.e., tarextumab or placebo) up to 30 days following the last administration of any study drug. AE severity was rated by the investigator according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.03 criteria.


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A high-level safety summary will display the numbers of patients within each treatment arm who experience one or more AEs in each of the following categories:

All TEAEs regardless of severity or presumed relationship to study drug

TEAEs judged related to tarextumab/placebo

TEAEs judged related to etoposide

TEAEs judged related to platinum therapy (cisplatin or carboplatin)

TEAEs judged related to any study drug

Treatment-emergent SAEs regardless of severity or presumed relationship to study drug

Treatment-emergent SAEs judged related to tarextumab

Treatment-emergent SAEs judged related to EP

Treatment-emergent SAEs judged related to any study drug

TEAEs leading to a delay/interruption in the administration of study drug

TEAEs leading to a reduction in the protocol-specified dose of study drug

TEAEs leading to discontinuation of study drug

TEAEs leading to withdrawal from the study

TEAEs leading to death The base summary of TEAEs will show treatment-arm incidence rates for each MedDRA primary system organ class (SOC) and/or preferred term (PT) sorted by descending incidence in the tarextumab treatment group. A separate summary will be produced for each of the AE subsets listed above. Additional summaries will be produced by CTCAE severity grade. Patients may have more than one TEAE per MedDRA SOC and/or PT. At each level of summarization, a patient is counted once if he or she reported one or more TEAEs at that level. In AE summaries by CTCAE severity grade, patients will be classified according to the highest reported CTCAE severity for a qualifying event.

11.3. Clinical Laboratory Parameters Clinical laboratory results (serum chemistry, hematology, coagulation and urinalysis) will be valued using conventional units of measurement and summarized by treatment group using descriptive statistics for baseline, maximum post baseline, minimum post baseline, and last observed values. Changes from baseline will also be summarized. All clinical laboratory results will be listed by patient.

The numbers of patients shifting from a ‘low’ or ‘normal’ test result at baseline to ‘high’ result at any post-baseline assessment will be summarized, as will the numbers of patients shifting from a ‘normal’ or ‘high’ result at baseline to ‘low’ result post baseline. Laboratory parameters with a CTCAE grading scale will be summarized in Range Change Abnormal (RCA) tables which categorize patients according to (1) their most extreme post-baseline severity grade, and (2) the severity grade at their last post-baseline evaluation. Parameters with a CTCAE grading scale for high values and a second scale for low values will be summarized in both directions. Some


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urinalysis parameters with categorical outcomes will be summarized with the numbers of patients shifting from normal at baseline (e.g., negative or absent) to an abnormal result post baseline (e.g., positive or present).

11.4. Vital Signs Vital signs (systolic and diastolic blood pressures, pulse, body temperature and respiration rate) will be summarized by treatment group using descriptive statistics for baseline, maximum post baseline, minimum post baseline, and last observed values. Changes from baseline will also be summarized. All vital signs will be listed by patient.

The numbers of patients with a result above the normal range at any post-baseline assessment will be summarized, as will the numbers of patients with a result below the normal range at any post-baseline visit. Normal ranges are:

Systolic blood pressure: 90-120 mm Hg

Diastolic blood pressure: 60-80 mm Hg

Pulse rate: 60-100 beats/minute

Body temperature: 97.8-99.1 °F

Respiratory rate: 12-18 breaths/minute

11.5. Electrocardiogram Results ECG results (QRS duration, PR interval and QTc Interval) will be summarized by treatment group using descriptive statistics for baseline, maximum post baseline, minimum post baseline, and last observed values. Changes from baseline will also be summarized. All ECG results will be listed by patient.

The numbers of patients with a result above the normal range at any post-baseline assessment will be summarized, as will the numbers of patients with a result below the normal range at any post-baseline visit. Normal ranges are:

QRS duration: 80-100 msec

PR interval: 120-200 msec

QTc interval (Bazett or Fridericia formula): ≤430 msec for males; ≤450 msec for females The numbers of QTc values in the ranges <480 msec; 480-500 msec; and >500 msec will be presented for the categories baseline, worst (maximum) post-baseline assessment, and last post-baseline assessment.

The overall clinical interpretation of each ECG acquisition will be classified on the ordinal scale normal, abnormal but not clinically significant, and abnormal with clinical significance. Overall clinical interpretation will then be summarized (1) for the categories baseline, worst (maximum) post-baseline assessment, and last post-baseline assessment and (2) in a shift table pairing the baseline and most extreme post-baseline classifications.


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11.6. ECOG Performance Status ECOG performance status will be summarized (1) for the categories baseline, minimum post-baseline value, maximum post-baseline value, and last post-baseline value and (2) in a shift table pairing the baseline assessment and most extreme post-baseline values.

11.7. Immunogenicity The incidence of anti-tarextumab antibody development in the tarextumab treatment group will be summarized with counts and proportions. In addition, the impact of detectable anti-tarextumab antibodies and neutralizing anti-tarextumab antibodies on the efficacy of tarextumab will be assessed by summarizing PFS and OS in the subgroups of patients with and without these anti-tarextumab antibodies. The impact of detectable anti-tarextumab antibodies and neutralizing anti-tarextumab antibodies on the safety of tarextumab will be assessed by comparing AE incidence rates in the subgroups of patients with and without these anti-tarextumab antibodies. However, these subgroup analyses may not be carried out if the number of subjects with or without anti-tarextumab antibodies does not provide reasonable estimates of PFS and ORR.

11.8. Prior and Concomitant Medications Medications recorded on case report forms will be mapped to Anatomical/Therapeutic/Chemical (ATC) classes and preferred names in the World Health Organization (WHO) Drug Dictionary Enhanced (version March 1, 2014).

Prior and concomitant medications will be summarized for each treatment group by WHO ATC class and preferred name. Patients may have used more than one prior/concomitant medication per ATC class and preferred name. At each level of summarization, a patient is counted once if he or she reported one or more medications at that level. Summaries will be ordered by descending order of incidence of ATC class and preferred name within each ATC class. All prior and concomitant medications will be listed by patient.

12. REFERENCES 1. Eisenhauer EA, Therasse P, Bogaerts J, et al. New response evaluation criteria in solid

tumors: Revised RECIST guideline (version 1.1). Eur J Cancer. 2009;45:228-247.

2. Noda K, Nishiwaki Y, Kawahara M, et al. Irinotecan plus cisplatin compared with etoposide plus cisplatin for extensive small-cell lung cancer. N Engl J Med. 2002;346(2): 85-91.

3. Hanna N, Bunn PA Jr, Langer C, et al. Randomized Phase III Trial Comparing Irinotecan/Cisplatin With Etoposide/Cisplatin in Patients With Previously Untreated Extensive-Stage Disease Small-Cell Lung Cancer. J Clin Oncol. 2006;24(13):2038-2043.


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Appendix A. List of Tables, Figures and Listings

List of Tables

Table Number

Table Description

14.1 DEMOGRAPHIC DATA 14.1.1.1 Subject Disposition (All Subjects) 14.1.1.2 Platinum Therapy Randomization Strata Versus Actual Platinum Therapy

Received (ITT Population) 14.1.2 Protocol Deviations 14.1.2.1 Major Protocol Deviations (ITT Population) 14.1.3 Demographics and Baseline 14.1.3.1 Demographic Characteristics (ITT Population) 14.1.3.2 Demographic Characteristics (Safety Population) 14.1.3.3 Demographic Characteristics (Per-Protocol Population) 14.1.3.4 Demographic Characteristics (Immunogenicity Population) 14.1.3.5 Baseline Characteristics (ITT Population) 14.1.3.6 Baseline Characteristics (Safety Population) 14.1.3.7 Baseline Characteristics (Per-Protocol Population) 14.1.3.8 Baseline Characteristics (Immunogenicity Population) 14.1.3.9 Small Cell Lung Cancer Disease Characteristics (ITT Population) 14.1.3.10 Small Cell Lung Cancer Disease Characteristics (Safety Population) 14.1.3.11 Prior Therapies for Small Cell Lung Cancer (ITT Population) 14.1.3.12 Prior Therapies for Small Cell Lung Cancer (Safety Population) 14.1.3.13 Baseline Gene Expression (ITT Population) 14.1.3.14 Baseline Gene Expression (Safety Population) 14.1.3.15 Baseline Gene Expression (Per-Protocol Population) 14.1.3.16 Prior and Concomitant Medications (Safety Population) 14.2 EFFICACY DATA 14.2.1 Overall Survival 14.2.1.1 Overall Survival (ITT Population) 14.2.1.2 Overall Survival (Per-Protocol Population) 14.2.1.3 Overall Survival for Patients Receiving Cisplatin (ITT Population) 14.2.1.4 Overall Survival for Patients Receiving Cisplatin (Per-Protocol Population) 14.2.1.5 Overall Survival for Patients Receiving Carboplatin (ITT Population) 14.2.1.6 Overall Survival for Patients Receiving Carboplatin (Per-Protocol

Population) 14.2.1.7 Overall Survival – Impact of Biomarker Expression (ITT Population) 14.2.1.8 Overall Survival – Impact of Biomarker Expression (Per-Protocol

Population) 14.2.1.9 Overall Survival – Impact of Notch3 Expression in Subjects with

High/Low Notch Pathway Markers (ITT Population) 14.2.1.10 Overall Survival – Impact of Notch3 Expression in Subjects with

High/Low Notch Pathway Markers (Per-Protocol Population) 14.2.2 Progression-Free Survival


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Table Number

Table Description

14.2.2.1 Progression-Free Survival – Primary Analysis (ITT Population) 14.2.2.2 Progression-Free Survival – Primary Analysis (Per-Protocol Population) 14.2.2.3 Progression-Free Survival During Combination Chemotherapy (ITT

Population) 14.2.2.4 Progression-Free Survival During Combination Chemotherapy (Per-

Protocol Population) 14.2.2.5 Progression-Free Survival – Impact of Biomarker Expression (ITT

Population) 14.2.2.6 Progression-Free Survival – Impact of Biomarker Expression (Per-Protocol

Population) 14.2.2.7 Progression-Free Survival – Impact of Notch3 Expression in Subjects with

High/Low Notch Pathway Markers (ITT Population) 14.2.2.8 Progression-Free Survival – Impact of Notch3 Expression in Subjects with

High/Low Notch Pathway Markers (Per-Protocol Population) 14.2.2.9 Progression-Free Survival – Sensitivity Analysis (Per-Protocol Population) 14.2.3 Landmark Survival 14.2.3.1 Landmark Survival at 180, 360, 540 and 720 Days (ITT Population) 14.2.3.2 Landmark Survival at 180, 360, 540 and 720 Days (Per-Protocol

Population) 14.2.4 Tumor Length 14.2.4.1 Summary Assessment of Tumor Length (ITT Population) 14.2.4.2 Summary Assessment of Tumor Length (Per-Protocol Population) 14.2.4.3 Rate of Change in Total Tumor Length at Progression (ITT Population) 14.2.4.4 Rate of Change in Total Tumor Length at Progression (Per-Protocol

Population) 14.2.4.5 Rate of Change from Total Tumor Length at Baseline (ITT Population) 14.2.4.6 Rate of Change from Total Tumor Length at Baseline (Per-Protocol

Population) 14.2.5 Best Overall Tumor Response 14.2.5.1 Best Overall Tumor Response Based on Investigator Assessment (ITT

Population) 14.2.5.2 Best Overall Tumor Response Based on Investigator Assessment (Per-

Protocol Population) 14.2.5.3 Best Overall Tumor Response Based on Investigator Assessment – Impact

of Biomarker Expression (ITT Population) 14.2.5.4 Best Overall Tumor Response Based on Investigator Assessment – Impact

of Biomarker Expression (Per-Protocol Population) 14.2.6 Duration of Response 14.2.6.1 Duration of Response (ITT Population) 14.2.6.2 Duration of Response (Per-Protocol Population) 14.2.7 Sites of Progression 14.2.7.1 Sites of Progression (ITT Population) 14.2.7.2 Sites of Progression (Per-Protocol Population)


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Table Number

Table Description

14.3 SAFETY DATA 14.3.1 Displays of Adverse Events 14.3.1.1 Overall Summary of Treatment-Emergent Adverse Events (TEAEs)

(Safety Population) 14.3.1.2 Treatment-Emergent Adverse Events (TEAEs) by System Organ Class and

Preferred Term (Safety Population) 14.3.1.3 Treatment-Emergent Adverse Events (TEAEs) Related to Study Drug by

MedDRA System Organ Class and Preferred Term (Safety Population) 14.3.1.4 Treatment-Emergent Adverse Events (TEAEs) Related to Etoposide by

MedDRA System Organ Class and Preferred Term (Safety Population) 14.3.1.5 Treatment-Emergent Adverse Events (TEAEs) Related to Platinum

Therapy by MedDRA System Organ Class and Preferred Term (Safety Population)

14.3.1.6 Treatment-Emergent Adverse Events (TEAEs) by System Organ Class, Preferred Term and CTCAE Severity Grade (Safety Population)

14.3.1.7 Treatment-Emergent Adverse Events (TEAEs) Related to Study Drug by System Organ Class, Preferred Term and CTCAE Severity Grade (Safety Population)

14.3.1.8 Treatment-Emergent Adverse Events (TEAEs) Related to Etoposide by System Organ Class, Preferred Term and CTCAE Severity Grade (Safety Population)

14.3.1.9 Treatment-Emergent Adverse Events (TEAEs) Related to Platinum Therapy by System Organ Class, Preferred Term and CTCAE Severity Grade (Safety Population)

14.3.1.10 Treatment-Emergent Adverse Events (TEAEs) by Preferred Term (Safety Population)

14.3.1.11 Treatment-Emergent Adverse Events (TEAEs) Related to Study Drug by Preferred Term (Safety Population)

14.3.1.12 Treatment-Emergent Adverse Events (TEAEs) Related to Etoposide by Preferred Term (Safety Population)

14.3.1.13 Treatment-Emergent Adverse Events (TEAEs) Related to Platinum Therapy by Preferred Term (Safety Population)

14.3.2 Deaths, Other Serious and Significant Adverse Events 14.3.2.1 Treatment-Emergent Adverse Events (TEAEs) with Outcome of Death by

System Organ Class and Preferred Term (Safety Population) 14.3.2.2 Serious Treatment-Emergent Adverse Events (TEAEs) by System Organ

Class and Preferred Term (Safety Population) 14.3.2.3 Serious Treatment-Emergent Adverse Events (TEAEs) Related to Study

Drug by System Organ Class and Preferred Term (Safety Population) 14.3.2.4 Serious Treatment-Emergent Adverse Events (TEAEs) Related to

Etoposide by System Organ Class and Preferred Term (Safety Population) 14.3.2.5 Serious Treatment-Emergent Adverse Events (TEAEs) Related to Platinum

Therapy by System Organ Class and Preferred Term (Safety Population)


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Table Number

Table Description

14.3.2.6 Treatment-Emergent Adverse Events (TEAEs) Leading to Delay/Interruption of Study Drug by System Organ Class and Preferred Term (Safety Population)

14.3.2.7 Treatment-Emergent Adverse Events (TEAEs) Leading to Delay/Interruption of Etoposide by System Organ Class and Preferred Term (Safety Population)

14.3.2.8 Treatment-Emergent Adverse Events (TEAEs) Leading to Delay/Interruption of Platinum Therapy by System Organ Class and Preferred Term (Safety Population)

14.3.2.9 Treatment-Emergent Adverse Events (TEAEs) Leading to Dose Reduction of Study Drug by System Organ Class and Preferred Term (Safety Population)

14.3.2.10 Treatment-Emergent Adverse Events (TEAEs) Leading to Dose Reduction of Etoposide by System Organ Class and Preferred Term (Safety Population)

14.3.2.11 Treatment-Emergent Adverse Events (TEAEs) Leading to Dose Reduction of Platinum Therapy by System Organ Class and Preferred Term (Safety Population)

14.3.2.12 Treatment-Emergent Adverse Events (TEAEs) Leading to Withdrawal of Study Drug by System Organ Class and Preferred Term (Safety Population)

14.3.2.13 Treatment-Emergent Adverse Events (TEAEs) Leading to Withdrawal of Etoposide by System Organ Class and Preferred Term (Safety Population)

14.3.2.14 Treatment-Emergent Adverse Events (TEAEs) Leading to Withdrawal of Platinum Therapy by System Organ Class and Preferred Term (Safety Population)

14.3.2.15 Treatment-Emergent Adverse Events (TEAEs) Leading to Discontinuation of Study Drug by System Organ Class and Preferred Term (Safety Population)

14.3.2.16 Treatment-Emergent Adverse Events (TEAEs) with Outcome of Death by Preferred Term (Safety Population)

14.3.2.17 Serious Treatment-Emergent Adverse Events (TEAEs) by Preferred Term (Safety Population)

14.3.2.18 Serious Treatment-Emergent Adverse Events (TEAEs) Related to Study Drug by Preferred Term (Safety Population)

14.3.2.19 Serious Treatment-Emergent Adverse Events (TEAEs) Related to Etoposide by Preferred Term (Safety Population)

14.3.2.20 Serious Treatment-Emergent Adverse Events (TEAEs) Related to Platinum Therapy by Preferred Term (Safety Population)

14.3.2.21 Treatment-Emergent Adverse Events (TEAEs) Leading to Delay/Interruption of Study Drug by Preferred Term (Safety Population)

14.3.2.22 Treatment-Emergent Adverse Events (TEAEs) Leading to Delay/Interruption of Etoposide by Preferred Term (Safety Population)


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Table Number

Table Description

14.3.2.23 Treatment-Emergent Adverse Events (TEAEs) Leading to Delay/Interruption of Platinum Therapy by Preferred Term (Safety Population)

14.3.2.24 Treatment-Emergent Adverse Events (TEAEs) Leading to Dose Reduction of Study Drug by Preferred Term (Safety Population)

14.3.2.25 Treatment-Emergent Adverse Events (TEAEs) Leading to Dose Reduction of Etoposide by Preferred Term (Safety Population)

14.3.2.26 Treatment-Emergent Adverse Events (TEAEs) Leading to Dose Reduction of Platinum Therapy by Preferred Term (Safety Population)

14.3.2.27 Treatment-Emergent Adverse Events (TEAEs) Leading to Withdrawal of Study Drug by Preferred Term (Safety Population)

14.3.2.28 Treatment-Emergent Adverse Events (TEAEs) Leading to Withdrawal of Etoposide by Preferred Term (Safety Population)

14.3.2.29 Treatment-Emergent Adverse Events (TEAEs) Leading to Withdrawal of Platinum Therapy by Preferred Term (Safety Population)

14.3.2.30 Treatment-Emergent Adverse Events (TEAEs) Leading to Discontinuation of Study Drug by Preferred Term (Safety Population)

14.3.2.31 Serious Treatment-Emergent Adverse Events (TEAEs) by System Organ Class, Preferred Term and CTCAE Severity Grade (Safety Population)

14.3.2.32 Serious Treatment-Emergent Adverse Events (TEAEs) Related to Study Drug by System Organ Class, Preferred Term and CTCAE Severity Grade (Safety Population)

14.3.2.33 Serious Treatment-Emergent Adverse Events (TEAEs) Related to Etoposide by System Organ Class, Preferred Term and CTCAE Severity Grade (Safety Population)

14.3.2.34 Serious Treatment-Emergent Adverse Events (TEAEs) Related to Platinum Therapy by System Organ Class, Preferred Term and CTCAE Severity Grade (Safety Population)

14.3.4 Laboratory and Other Data 14.3.4.1 Hematology (Safety Population) 14.3.4.2 Hematology – Shift from Baseline (Safety Population) 14.3.4.3 Hematology – Range Change Abnormal – High (Safety Population) 14.3.4.4 Hematology – Range Change Abnormal – Low (Safety Population) 14.3.4.5 Serum Chemistry (Safety Population) 14.3.4.6 Serum Chemistry – Shift from Baseline (Safety Population) 14.3.4.7 Serum Chemistry – Range Change Abnormal – High (Safety Population) 14.3.4.8 Serum Chemistry – Range Change Abnormal – Low (Safety Population) 14.3.4.9 Coagulation (Safety Population) 14.3.4.10 Coagulation– Shift from Baseline (Safety Population) 14.3.4.11 Coagulation– Range Change Abnormal – High (Safety Population) 14.3.4.12 Urinalysis (Safety Population) 14.3.4.13 Urinalysis – Shift from Baseline (Safety Population) 14.3.4.14 Vital Signs (Safety Population)


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Table Number

Table Description

14.3.4.15 Vital Signs – Range Change Abnormal (RCA) (Safety Population) 14.3.4.16 12-Lead Electrocardiogram (ECG) (Safety Population) 14.3.4.17 12-Lead Electrocardiogram (ECG) – Range Change Abnormal (RCA)

(Safety Population) 14.3.4.18 12-Lead Electrocardiogram (ECG) – QTc Interval (Safety Population) 14.3.4.19 12-Lead Electrocardiogram (ECG) – Overall Interpretation (Safety

Population) 14.3.4.20 12-Lead Electrocardiogram (ECG) – Overall Interpretation Shift from

Baseline (Safety Population) 14.3.4.21 ECOG Performance Status (Safety Population) 14.3.4.22 ECOG Performance Status – Shift from Baseline (Safety Population) 14.3.4.23 Anti-Tarextumab Antibodies (Immunogenicity Population) 14.3.4.24 Impact of Anti-Tarextumab Antibodies on Progression-Free Survival

(Immunogenicity Population) 14.3.4.25 Impact of Anti-Tarextumab Antibodies on Overall Survival

(Immunogenicity Population) 14.3.4.26 Overall Summary of Impact of Anti-Tarextumab Antibodies on Treatment-

Emergent Adverse Events (TEAEs) (Immunogenicity Population) 14.3.4.27 Impact of Anti-Tarextumab Antibodies Treatment-Emergent Adverse

Events (TEAEs) (Immunogenicity Population) 14.3.5 Extent of Exposure 14.3.5.1 Study Drug Exposure – Tarextumab/Placebo (Safety Population) 14.3.5.2 Dosing Compliance – Tarextumab/Placebo (Safety Population) 14.3.5.3 Study Drug Exposure – Etoposide (Safety Population) 14.3.5.4 Dosing Compliance – Etoposide (Safety Population) 14.3.5.5 Study Drug Exposure – Cisplatin (Safety Population) 14.3.5.6 Dosing Compliance – Cisplatin (Safety Population) 14.3.5.7 Study Drug Exposure – Carboplatin (Safety Population) 14.3.5.8 Dosing Compliance – Carboplatin (Safety Population)


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List of Figures

Figure Number

Figure Description

14.2.1.1 Overall Survival (ITT Population) 14.2.1.2 Overall Survival (ITT Population with Notch3 >25th Percentile) 14.2.1.3 Overall Survival (ITT Population with Notch3 >50th Percentile) 14.2.1.4 Overall Survival (ITT Population with Notch3 >75th Percentile) 14.2.1.5 Overall Survival (ITT Population with Hes1 >25th Percentile) 14.2.1.6 Overall Survival (ITT Population with Hes1 >50th Percentile) 14.2.1.7 Overall Survival (ITT Population with Hes1 >75th Percentile) 14.2.1.8 Overall Survival (ITT Population with Hes6 >25th Percentile) 14.2.1.9 Overall Survival (ITT Population with Hes6 >50th Percentile) 14.2.1.10 Overall Survival (ITT Population with Hes6 >75th Percentile) 14.2.1.11 Overall Survival (ITT Population with Hey1 >25th Percentile) 14.2.1.12 Overall Survival (ITT Population with Hey1 >50th Percentile) 14.2.1.13 Overall Survival (ITT Population with Hey1 >75th Percentile) 14.2.1.14 Overall Survival (ITT Population with Hey2 >25th Percentile) 14.2.1.15 Overall Survival (ITT Population with Hey2 >50th Percentile) 14.2.1.16 Overall Survival (ITT Population with Hey2 >75th Percentile) 14.2.1.17 Overall Survival (Per-Protocol Population) 14.2.2.1 Progression-Free Survival (ITT Population) 14.2.2.2 Progression-Free Survival (ITT Population with Notch3 >25th Percentile) 14.2.2.3 Progression-Free Survival (ITT Population with Notch3 >50th Percentile) 14.2.2.4 Progression-Free Survival (ITT Population with Notch3 >75th Percentile) 14.2.2.5 Progression-Free Survival (ITT Population with Hes1 >25th Percentile) 14.2.2.6 Progression-Free Survival (ITT Population with Hes1 >50th Percentile) 14.2.2.7 Progression-Free Survival (ITT Population with Hes1 >75th Percentile) 14.2.2.8 Progression-Free Survival (ITT Population with Hes6 >25th Percentile) 14.2.2.9 Progression-Free Survival (ITT Population with Hes6 >50th Percentile) 14.2.2.10 Progression-Free Survival (ITT Population with Hes6 >75th Percentile) 14.2.2.11 Progression-Free Survival (ITT Population with Hey1 >25th Percentile) 14.2.2.12 Progression-Free Survival (ITT Population with Hey1 >50th Percentile) 14.2.2.13 Progression-Free Survival (ITT Population with Hey1 >75th Percentile) 14.2.2.14 Progression-Free Survival (ITT Population with Hey2 >25th Percentile) 14.2.2.15 Progression-Free Survival (ITT Population with Hey2 >50th Percentile) 14.2.2.16 Progression-Free Survival (ITT Population with Hey2 >75th Percentile) 14.2.2.17 Progression-Free Survival (Per-Protocol Population) 14.2.4.1 Waterfall Plot of Best Percentage Change from Baseline Total Tumor

Length [ITT Population] 14.2.4.2 Waterfall Plot of Best Percentage Change from Baseline Total Tumor

Length [Per-Protocol Population] 14.2.6.1 Duration of Response (ITT Population) 14.2.6.2 Duration of Response (Per-Protocol Population) 14.3.4.1 Box Plot of Hemoglobin by Visit (Safety Population)


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Figure Number

Figure Description

14.3.4.2 Box Plot of Change from Baseline Hemoglobin by Visit (Safety Population)

14.3.4.3 Box Plot of Hematocrit by Visit (Safety Population) 14.3.4.4 Box Plot of Change from Baseline Hematocrit by Visit (Safety Population) 14.3.4.5 Box Plot of Platelets by Visit (Safety Population) 14.3.4.6 Box Plot of Change from Baseline Platelets by Visit (Safety Population) 14.3.4.7 Box Plot of Red Blood Cells by Visit (Safety Population) 14.3.4.8 Box Plot of Change from Baseline Red Blood Cells by Visit (Safety

Population) 14.3.4.9 Box Plot of White Blood Cells by Visit (Safety Population) 14.3.4.10 Box Plot of Change from Baseline White Blood Cells by Visit (Safety

Population) 14.3.4.11 Box Plot of Absolute Neutrophil Count by Visit (Safety Population) 14.3.4.12 Box Plot of Change from Baseline Absolute Neutrophil Count by Visit

(Safety Population) 14.3.4.13 Box Plot of Albumin by Visit (Safety Population) 14.3.4.14 Box Plot of Change from Baseline Albumin by Visit (Safety Population) 14.3.4.15 Box Plot of Alkaline Phosphatase by Visit (Safety Population) 14.3.4.16 Box Plot of Change from Baseline Alkaline Phosphatase by Visit (Safety

Population) 14.3.4.17 Box Plot of Total Bilirubin by Visit (Safety Population) 14.3.4.18 Box Plot of Change from Baseline Total Bilirubin by Visit (Safety

Population) 14.3.4.19 Box Plot of Direct Bilirubin by Visit (Safety Population) 14.3.4.20 Box Plot of Change from Baseline Direct Bilirubin by Visit (Safety

Population) 14.3.4.21 Box Plot of Bicarbonate by Visit (Safety Population) 14.3.4.22 Box Plot of Change from Baseline Bicarbonate by Visit (Safety

Population) 14.3.4.23 Box Plot of Blood Urea Nitrogen by Visit (Safety Population) 14.3.4.24 Box Plot of Change from Baseline Blood Urea Nitrogen by Visit (Safety

Population) 14.3.4.25 Box Plot of Calcium by Visit (Safety Population) 14.3.4.26 Box Plot of Change from Baseline Calcium by Visit (Safety Population) 14.3.4.27 Box Plot of Chloride by Visit (Safety Population) 14.3.4.28 Box Plot of Change from Baseline Chloride by Visit (Safety Population) 14.3.4.29 Box Plot of Creatinine by Visit (Safety Population) 14.3.4.30 Box Plot of Change from Baseline Creatinine by Visit (Safety Population) 14.3.4.31 Box Plot of Glucose by Visit (Safety Population) 14.3.4.32 Box Plot of Change from Baseline Glucose by Visit (Safety Population) 14.3.4.33 Box Plot of Lactic Dehydrogenase by Visit (Safety Population) 14.3.4.34 Box Plot of Change from Baseline Lactic Dehydrogenase by Visit (Safety

Population)


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Figure Number

Figure Description

14.3.4.35 Box Plot of Magnesium by Visit (Safety Population) 14.3.4.36 Box Plot of Change from Baseline Magnesium by Visit (Safety Population) 14.3.4.37 Box Plot of Phosphorus by Visit (Safety Population) 14.3.4.38 Box Plot of Change from Baseline Phosphorus by Visit (Safety Population) 14.3.4.39 Box Plot of Potassium by Visit (Safety Population) 14.3.4.40 Box Plot of Change from Baseline Potassium by Visit (Safety Population) 14.3.4.41 Box Plot of Total Protein by Visit (Safety Population) 14.3.4.42 Box Plot of Change from Baseline Total Protein by Visit (Safety

Population) 14.3.4.43 Box Plot of AST (SGOT) by Visit (Safety Population) 14.3.4.44 Box Plot of Change from Baseline AST (SGOT) by Visit (Safety

Population) 14.3.4.45 Box Plot of ALT (SGPT) by Visit (Safety Population) 14.3.4.46 Box Plot of Change from Baseline ALT (SGPT) by Visit (Safety

Population) 14.3.4.47 Box Plot of Sodium by Visit (Safety Population) 14.3.4.48 Box Plot of Change from Baseline Sodium by Visit (Safety Population) 14.3.4.49 Box Plot of Phosphorus by Visit (Safety Population) 14.3.4.50 Box Plot of Change from Baseline Phosphorus by Visit (Safety Population) 14.3.4.51 Box Plot of International Normalized Ratio by Visit (Safety Population) 14.3.4.52 Box Plot of Change from Baseline International Normalized Ratio by Visit

(Safety Population) 14.3.4.53 Box Plot of Prothrombin Time by Visit (Safety Population) 14.3.4.54 Box Plot of Change from Baseline Prothrombin Time by Visit (Safety

Population) 14.3.4.55 Box Plot of Activated Partial Thromboplastin Time by Visit (Safety

Population) 14.3.4.56 Box Plot of Change from Baseline Activated Partial Thromboplastin Time

by Visit (Safety Population) 14.3.4.57 Box Plot of pH by Visit (Safety Population) 14.3.4.58 Box Plot of Change from Baseline pH by Visit (Safety Population) 14.3.4.59 Box Plot of Specific Gravity by Visit (Safety Population) 14.3.4.60 Box Plot of Change from Baseline Specific Gravity by Visit (Safety

Population) 14.3.4.61 Box Plot of Temperature by Visit (Safety Population) 14.3.4.62 Box Plot of Change from Baseline Temperature by Visit (Safety

Population) 14.3.4.63 Box Plot of Pulse Rate by Visit (Safety Population) 14.3.4.64 Box Plot of Change from Baseline Pulse Rate by Visit (Safety Population) 14.3.4.65 Box Plot of Respiratory Rate by Visit (Safety Population) 14.3.4.66 Box Plot of Change from Baseline Respiratory Rate by Visit (Safety

Population) 14.3.4.67 Box Plot of Systolic Blood Pressure by Visit (Safety Population)


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Figure Number

Figure Description

14.3.4.68 Box Plot of Change from Baseline Systolic Blood Pressure by Visit (Safety Population)

14.3.4.69 Box Plot of Diastolic Blood Pressure by Visit (Safety Population) 14.3.4.70 Box Plot of Change from Baseline Diastolic Blood Pressure by Visit

(Safety Population) 14.3.4.71 Box Plot of Weight by Visit (Safety Population) 14.3.4.72 Box Plot of Change from Baseline Weight by Visit (Safety Population) 14.3.4.73 Box Plot of QRS Duration by Visit (Safety Population) 14.3.4.74 Box Plot of Change from Baseline QRS Duration by Visit (Safety

Population) 14.3.4.75 Box Plot of PR Interval by Visit (Safety Population) 14.3.4.76 Box Plot of Change from Baseline PR Interval by Visit (Safety Population) 14.3.4.77 Box Plot of QTc Interval by Visit (Safety Population) 14.3.4.78 Box Plot of Change from Baseline QTc Interval by Visit (Safety

Population)


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List of Listings

Listing Number

Listing Description

16.2.1 Discontinued Subjects 16.2.1.1 Subject Disposition 16.2.1.2 Informed Consent 16.2.2 Protocol Deviations 16.2.2.1 Major Protocol Deviations 16.2.3 Subjects Excluded from Efficacy Analyses 16.2.3.1 Inclusion/Exclusion Criteria 16.2.4 Demographics and Other Data 16.2.4.1 Demographics and Baseline Characteristics 16.2.4.2 Medical/Surgical History 16.2.4.3 Extensive Small Cell Lung Cancer History 16.2.4.4 Prior Surgery for Lung Cancer 16.2.4.5 Prior Radiotherapy for Lung Cancer 16.2.4.6 Baseline Gene Expression 16.2.4.7 FFPE Tissue Sample 16.2.4.8 Prior and Concomitant Medications 16.2.4.9 Concomitant Procedures 16.2.5 Compliance and Drug Concentration Data 16.2.5.1 Study Drug Infusion 16.2.5.2 Etoposide Infusion 16.2.5.3 Platinum Therapy Infusion 16.2.5.4 Doses Delayed, Interrupted, Reduced and Not Administered 16.2.5.5 Pre-dose, Post-dose and Single PK Samples 16.2.6 Efficacy Data 16.2.6.2 Tumor Evaluations – Target Lesions 16.2.6.3 Tumor Evaluations – Non-target Lesions 16.2.6.4 Tumor Evaluations – New Lesions 16.2.6.5 Tumor Assessments (RECIST Overall Response) 16.2.6.6 Derived Efficacy Data 16.2.6.7 End of Treatment 16.2.7 Adverse Events 16.2.7.1 Adverse Events 16.2.7.2 Deaths 16.2.7.3 Serious Adverse Events 16.2.7.4 Adverse Events Leading to Study Drug Discontinuation 16.2.8 Laboratory and Other Data 16.2.8.1 Hematology 16.2.8.2 PT/INR and aPTT 16.2.8.3 Serum Chemistry 16.2.8.4 Urinalysis 16.2.8.5 Vital Signs


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Listing Number

Listing Description

16.2.8.6 ECOG Performance Status 16.2.8.7 12-Lead ECG 16.2.8.8 Physical Examination 16.2.8.9 Optional Blood for Pharmacogenomics 16.2.8.10 CA19-9 Tumor Marker 16.2.8.11 Anti-Tarextumab Antibodies 16.2.8.12 Blood for Biomarkers 16.2.8.13 Serum Pregnancy Test 16.2.8.14 Optional Tumor Core Biopsy 16.2.8.15 On Study PCI or WBRT (PCI) 16.2.8.16 Follow up after Discontinuation of Study Treatment 16.2.8.17 Treatments and Procedures for Extensive Small Cell Lung Cancer During

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al A

naly

sis P

lan

59R

5-00

3 (P

hase

2)

23

MA

R20

17

Conf

iden

tial

Pa

ge 4

5/14

9

Onc

oMed

Pha

rmac

eutic

als,

Inc.

Page

1 o

f x

59R

5-00

3 (P

hase

2)

Tab

le 1

4.1.

1.1

Su

bjec

t Dis

posi

tion

A

ll Su

bjec

ts

Pl

aceb

o Ta

rext

umab

To

tal

Subj

ects

Ran

dom

ized

xx

xx

xx

IT

T Po

pula

tion[1

] xx

(xx.

x%)

xx (x

x.x%

) xx

(xx.

x%)

Per-P

roto

col P

opul

atio

n[2]

xx (x

x.x%

) xx

(xx.

x%)

xx (x

x.x%

) Sa

fety

Pop

ulat

ion[3

] xx

(xx.

x%)

xx (x

x.x%

) xx

(xx.

x%)

Imm

unog

enic

ity P

opul

atio

n[4]

xx (x

x.x%

) xx

(xx.

x%)

xx (x

x.x%

) Ph

arm

acok

inet

ic P

opul

atio

n[5]

xx (x

x.x%

) xx

(xx.

x%)

xx (x

x.x%

)

Su

bjec

ts D

isco

ntin

ued

xx

xx

xx

Prim

ary

Rea

son

for S

tudy

Exi

t

D

eath

xx

(xx.

x%)

xx (x

x.x%

) xx

(xx.

x%)

Lo

st to

Fol

low

-Up

xx (x

x.x%

) xx

(xx.

x%)

xx (x

x.x%

)

Stud

y Te

rmin

ated

by

Onc

oMed

xx

(xx.

x%)

xx (x

x.x%

) xx

(xx.

x%)

W

ithdr

awal

by

Subj

ect

xx (x

x.x%

) xx

(xx.

x%)

xx (x

x.x%

)

Oth

er

xx (x

x.x%

) xx

(xx.

x%)

xx (x

x.x%

)

Pr

imar

y R

easo

n fo

r Dis

cont

inui

ng S

tudy

Dru

g [6

]

A

dver

se E

vent

xx

(xx.

x%)

xx (x

x.x%

) xx

(xx.

x%)

D

eath

xx

(xx.

x%)

xx (x

x.x%

) xx

(xx.

x%)

Lo

st to

Fol

low

-Up

xx (x

x.x%

) xx

(xx.

x%)

xx (x

x.x%

)

Dis

ease

Pro

gres

sion

xx

(xx.

x%)

xx (x

x.x%

) xx

(xx.

x%)

St

udy

Term

inat

ed b

y O

ncoM

ed

xx (x

x.x%

) xx

(xx.

x%)

xx (x

x.x%

)

With

draw

al o

f Con

sent

/ Pa

tient

Dec

isio

n xx

(xx.

x%)

xx (x

x.x%

) xx

(xx.

x%)

In

vest

igat

or D

ecis

ion

xx (x

x.x%

) xx

(xx.

x%)

xx (x

x.x%

)

Oth

er

xx (x

x.x%

) xx

(xx.

x%)

xx (x

x.x%

)

N

ote:

Den

omin

ator

s are

bas

ed o

n th

e IT

T po

pula

tion.

[1

] ITT

= In

tent

-to-T

reat

. ITT

pop

ulat

ion

is c

ompr

ised

of a

ll ra

ndom

ized

subj

ects

. [2

] All

rand

omiz

ed su

bjec

ts w

ho re

ceiv

ed a

t lea

st o

ne d

ose

of st

udy

drug

and

had

at l

east

one

pos

t bas

elin

e tu

mor

ass

essm

ent.

[3] A

ll su

bjec

ts w

ho re

ceiv

ed a

t lea

st o

ne p

artia

l dos

e of

tare

xtum

ab o

r pla

cebo

. [4

] All

subj

ects

who

had

a b

asel

ine

and

at le

ast o

ne fo

llow

-up

anti-

tare

xtum

ab a

ntib

ody

sam

ple

obta

ined

. [5

] All

subj

ects

who

rece

ived

at l

east

one

dos

e of

stud

y dr

ug a

nd h

ad a

t lea

st o

ne p

ost-d

ose

PK sa

mpl

e.

[6] St

udy

drug

is P

lace

bo o

r Tar

extu

mab

. [7

] Plat

inum

ther

apy

is c

ispl

atin

or c

arbo

plat

in.

Prog

ram

mer

Not

es: (

a) a

dd a

dditi

onal

set o

f row

s for

(i) “

Prim

ary

Reas

on fo

r Dis

cont

inui

ng E

topo

side”

and

(ii)

“Pri

mar

y Re

ason

for D

isco

ntin

uing

Pla

tinum

The

rapy

[7] ”

Onc

oMed

Pha

rmac

eutic

als,

Inc.

Stat

istic

al A

naly

sis P

lan

59R

5-00

3 (P

hase

2)

23

MA

R20

17

Conf

iden

tial

Pa

ge 4

6/14

9

Onc

oMed

Pha

rmac

eutic

als,

Inc.

Page

1 o

f x

59R

5-00

3 (P

hase

2)

Tab

le 1

4.1.

1.2

Pl

atin

um T

hera

py R

ando

miz

atio

n St

rata

Ver

sus A

ctua

l Pla

tinum

The

rapy

Rec

eive

d

ITT

Pop

ulat

ion

Act

ual P

latin

um T

hera

py R

ecei

ved

Pl

aceb

o (N

=xx)

Ta

rext

umab

(N

=xx)

To

tal

(N=x

x)

Cis

plat

in

Car

bopl

atin

C

ispl

atin

C

arbo

plat

in

Cis

plat

in

Car

bopl

atin

Pl

atin

um T

hera

py R

ando

miz

atio

n St

rata

Cis

plat

in

xx (x

x.x%

) xx

(xx.

x%)

xx (x

x.x%

) xx

(xx.

x%)

xx (x

x.x%

) xx

(xx.

x%)

C

arbo

plat

in

xx (x

x.x%

) xx

(xx.

x%)

xx (x

x.x%

) xx

(xx.

x%)

xx (x

x.x%

) xx

(xx.

x%)

Onc

oMed

Pha

rmac

eutic

als,

Inc.

Stat

istic

al A

naly

sis P

lan

59R

5-00

3 (P

hase

2)

23

MA

R20

17

Conf

iden

tial

Pa

ge 4

7/14

9

Onc

oMed

Pha

rmac

eutic

als,

Inc.

Page

1 o

f x

59R

5-00

3 (P

hase

2)

Tab

le 1

4.1.

2.1

M

ajor

Pro

toco

l Dev

iatio

ns

IT

T P

opul

atio

n

Pl

aceb

o (N

=xx)

Ta

rext

umab

(N

=xx)

To

tal

(N=x

x)

Any

Maj

or P

roto

col D

evia

tions

[1]

xx (x

x.x%

) xx

(xx.

x%)

xx (x

x.x%

)

Dev

iatio

n C

ateg

ory

1 xx

(xx.

x%)

xx (x

x.x%

) xx

(xx.

x%)

D

evia

tion

Cat

egor

y 2

xx (x

x.x%

) xx

(xx.

x%)

xx (x

x.x%

)

Dev

iatio

n C

ateg

ory

3 xx

(xx.

x%)

xx (x

x.x%

) xx

(xx.

x%)

Et

c.

xx (x

x.x%

) xx

(xx.

x%)

xx (x

x.x%

)

[1

] Su

bjec

ts m

ay b

e in

clud

ed in

mor

e th

an o

ne p

roto

col d

evia

tion

cate

gory

. Pr

ogra

mm

er n

ote:

the

act

ual c

ateg

orie

s of M

ajor

Pro

toco

l Dev

iatio

n wi

ll be

acc

ordi

ng to

the

exte

rnal

pro

toco

l dev

iatio

n fil

e re

ceiv

ed.

Onc

oMed

Pha

rmac

eutic

als,

Inc.

Stat

istic

al A

naly

sis P

lan

59R

5-00

3 (P

hase

2)

23

MA

R20

17

Conf

iden

tial

Pa

ge 4

8/14

9

Onc

oMed

Pha

rmac

eutic

als,

Inc.

Page

1 o

f x

59R

5-00

3 (P

hase

2)

Tab

le 1

4.1.

3.1

D

emog

raph

ic C

hara

cter

istic

s

ITT

Pop

ulat

ion

Pl

aceb

o (N

=xx)

Ta

rext

umab

(N

=xx)

To

tal

(N=x

x)

Age

(ye

ars)

[1]

n xx

xx

xx

Mea

n (S

D)

xx (x

x.x)

xx

(xx.

x)

xx (x

x.x)

Med

ian

xx

xx

xx

25

th, 7

5th P

erce

ntile

xx

, xx

xx, x

x xx

, xx

M

in, M

ax

xx, x

x xx

, xx

xx, x

x

Se

x

M

ale

xx (x

x.x%

) xx

(xx.

x%)

xx (x

x.x%

)

Fem

ale

xx (x

x.x%

) xx

(xx.

x%)

xx (x

x.x%

)

C

hild

Bea

ring

Pote

ntia

l [2

]

Y

es

xx (x

x.x%

) xx

(xx.

x%)

xx (x

x.x%

)

No

xx (x

x.x%

) xx

(xx.

x%)

xx (x

x.x%

)

Et

hnic

ity

His

pani

c or

Lat

ino

xx (x

x.x%

) xx

(xx.

x%)

xx (x

x.x%

)

Not

His

pani

c or

Lat

ino

xx (x

x.x%

) xx

(xx.

x%)

xx (x

x.x%

)

R

ace

Am

eric

an In

dian

or A

lask

a N

ativ

e xx

(xx.

x%)

xx (x

x.x%

) xx

(xx.

x%)

A

sian

xx

(xx.

x%)

xx (x

x.x%

) xx

(xx.

x%)

B

lack

or A

frica

n A

mer

ican

xx

(xx.

x%)

xx (x

x.x%

) xx

(xx.

x%)

N

ativ

e H

awai

ian

or O

ther

Pac

ific

Isla

nder

xx

(xx.

x%)

xx (x

x.x%

) xx

(xx.

x%)

W

hite

xx

(xx.

x%)

xx (x

x.x%

) xx

(xx.

x%)

Mul

tiple

Rac

es C

heck

ed

xx (x

x.x%

) xx

(xx.

x%)

xx (x

x.x%

)

[1

] Age

on

cons

ent d

ate.

[2

] For f

emal

es o

nly.

Prog

ram

mer

not

es: (

a) p

erce

ntag

es u

nder

Chi

ld B

eari

ng P

oten

tial a

re p

erce

ntag

es o

f fem

ale

subj

ects,

(b) r

epea

t thi

s tab

le u

sing

the

safe

ty, p

er-p

roto

col a

nd im

mun

ogen

icity

pop

ulat

ions

(c) r

emov

e ‘M

ultip

le R

aces

Che

cked

’ row

if a

ll ta

bles

hav

e ze

ro c

ount

for t

otal

.

Onc

oMed

Pha

rmac

eutic

als,

Inc.

Stat

istic

al A

naly

sis P

lan

59R

5-00

3 (P

hase

2)

23

MA

R20

17

Conf

iden

tial

Pa

ge 4

9/14

9

Onc

oMed

Pha

rmac

eutic

als,

Inc.

Page

1 o

f x

59R

5-00

3 (P

hase

2)

Tab

le 1

4.1.

3.5

B

asel

ine

Cha

ract

eris

tics

IT

T P

opul

atio

n

Pl

aceb

o (N

=xx)

Ta

rext

umab

(N

=xx)

To

tal

(N=x

x)

Hei

ght (

cm)

n xx

xx

xx

Mea

n (S

D)

xx (x

x.x)

xx

(xx.

x)

xx (x

x.x)

Med

ian

xx

xx

xx

25

th, 7

5th P

erce

ntile

xx

, xx

xx, x

x xx

, xx

M

in, M

ax

xx, x

x xx

, xx

xx, x

x

W

eigh

t (kg

)

n

xx

xx

xx

M

ean

(SD

) xx

(xx.

x)

xx (x

x.x)

xx

(xx.

x)

M

edia

n xx

xx

xx

25th

, 75th

Per

cent

ile

xx, x

x xx

, xx

xx, x

x

Min

, Max

xx

, xx

xx, x

x xx

, xx

Bod

y M

ass I

ndex

(kg/

m2 ) [1

]

n

xx

xx

xx

M

ean

(SD

) xx

(xx.

x)

xx (x

x.x)

xx

(xx.

x)

M

edia

n xx

xx

xx

25th

, 75th

Per

cent

ile

xx, x

x xx

, xx

xx, x

x

Min

, Max

xx

, xx

xx, x

x xx

, xx

ECO

G P

erfo

rman

ce S

tatu

s

0

xx (x

x.x%

) xx

(xx.

x%)

xx (x

x.x%

)

1 xx

(xx.

x%)

xx (x

x.x%

) xx

(xx.

x%)

2

xx (x

x.x%

) xx

(xx.

x%)

xx (x

x.x%

)

Sm

okin

g H

isto

ry

Nev

er S

mok

ed

xx (x

x.x%

) xx

(xx.

x%)

xx (x

x.x%

)

Ex S

mok

er

xx (x

x.x%

) xx

(xx.

x%)

xx (x

x.x%

)

Cur

rent

Sm

oker

xx

(xx.

x%)

xx (x

x.x%

) xx

(xx.

x%)

[1]

BM

I (kg

/m2 ) =

wei

ght (

kg) /

[hei

ght (

cm)]

2 . Pr

ogra

mm

er n

otes

: (a)

repe

at th

is ta

ble

usin

g th

e sa

fety

, per

-pro

toco

l and

imm

unog

enic

ity p

opul

atio

ns

Onc

oMed

Pha

rmac

eutic

als,

Inc.

Stat

istic

al A

naly

sis P

lan

59R

5-00

3 (P

hase

2)

23

MA

R20

17

Conf

iden

tial

Pa

ge 5

0/14

9

Onc

oMed

Pha

rmac

eutic

als,

Inc.

Page

1 o

f x

59R

5-00

3 (P

hase

2)

Tab

le 1

4.1.

3.9

Sm

all C

ell L

ung

Can

cer

Dis

ease

Cha

ract

eris

tics

IT

T P

opul

atio

n

Pl

aceb

o (N

=xx)

Ta

rext

umab

(N

=xx)

To

tal

(N=x

x)

Mon

ths S

ince

Dia

gnos

is [1

]

n

xx

xx

xx

M

ean

(SD

) xx

(xx.

x)

xx (x

x.x)

xx

(xx.

x)

M

edia

n xx

xx

xx

25th

, 75th

Per

cent

ile

xx, x

x xx

, xx

xx, x

x

Min

, Max

xx

, xx

xx, x

x xx

, xx

His

tolo

gica

l/Cyt

olog

ical

Typ

e

Sm

all C

ell O

nly

xx (x

x.x%

) xx

(xx.

x%)

xx (x

x.x%

)

Mix

ed T

ype

xx (x

x.x%

) xx

(xx.

x%)

xx (x

x.x%

)

Oth

er

xx (x

x.x%

) xx

(xx.

x%)

xx (x

x.x%

)

A

nato

mic

al L

ocat

ion

of P

rimar

y C

ance

r [1]

Rig

ht U

pper

Lun

g xx

(xx.

x%)

xx (x

x.x%

) xx

(xx.

x%)

R

ight

Low

er L

ung

xx (x

x.x%

) xx

(xx.

x%)

xx (x

x.x%

)

Mid

dle

of R

ight

Lun

g xx

(xx.

x%)

xx (x

x.x%

) xx

(xx.

x%)

Le

ft U

pper

Lun

g xx

(xx.

x%)

xx (x

x.x%

) xx

(xx.

x%)

O

ther

xx

(xx.

x%)

xx (x

x.x%

) xx

(xx.

x%)

Num

ber o

f Site

s of D

isea

se a

t Stu

dy E

ntry

1

xx (x

x.x%

) xx

(xx.

x%)

xx (x

x.x%

)

2 xx

(xx.

x%)

xx (x

x.x%

) xx

(xx.

x%)

≥3

xx

(xx.

x%)

xx (x

x.x%

) xx

(xx.

x%)

Site

s of D

isea

se a

t Stu

dy E

ntry

[2]

Bon

e xx

(xx.

x%)

xx (x

x.x%

) xx

(xx.

x%)

B

rain

xx

(xx.

x%)

xx (x

x.x%

) xx

(xx.

x%)

Pl

eura

xx

(xx.

x%)

xx (x

x.x%

) xx

(xx.

x%)

A

dren

al G

land

xx

(xx.

x%)

xx (x

x.x%

) xx

(xx.

x%)

Ly

mph

Nod

es

xx (x

x.x%

) xx

(xx.

x%)

xx (x

x.x%

)

Oth

er N

odes

xx

(xx.

x%)

xx (x

x.x%

) xx

(xx.

x%)

[1] M

onth

s sin

ce d

iagn

osis

to th

e da

te o

f ran

dom

izat

ion.

[2

] Su

bjec

ts m

ay b

e in

clud

ed in

mor

e th

an o

ne c

ateg

ory.

The

refo

re p

erce

ntag

es m

ay a

dd to

mor

e th

an 1

00%

.

Prog

ram

mer

not

es: (

a) re

peat

this

tabl

e us

ing

the

safe

ty p

opul

atio

n

Onc

oMed

Pha

rmac

eutic

als,

Inc.

Stat

istic

al A

naly

sis P

lan

59R

5-00

3 (P

hase

2)

23

MA

R20

17

Conf

iden

tial

Pa

ge 5

1/14

9

Onc

oMed

Pha

rmac

eutic

als,

Inc.

Page

1 o

f x

59R

5-00

3 (P

hase

2)

Tab

le 1

4.1.

3.11

Prio

r T

hera

pies

for

Smal

l Cel

l Lun

g C

ance

r

ITT

Pop

ulat

ion

Pl

aceb

o (N

=xx)

Ta

rext

umab

(N

=xx)

To

tal

(N=x

x)

Prio

r Sur

gery

for L

ung

Can

cer

Yes

xx

(xx.

x%)

xx (x

x.x%

) xx

(xx.

x%)

N

o xx

(xx.

x%)

xx (x

x.x%

) xx

(xx.

x%)

Prio

r Rad

ioth

erap

y fo

r Lun

g C

ance

r

Y

es

xx (x

x.x%

) xx

(xx.

x%)

xx (x

x.x%

)

No

xx (x

x.x%

) xx

(xx.

x%)

xx (x

x.x%

)

Prog

ram

mer

not

es: (

a) re

peat

this

tabl

e us

ing

the

safe

ty p

opul

atio

n

Onc

oMed

Pha

rmac

eutic

als,

Inc.

Stat

istic

al A

naly

sis P

lan

59R

5-00

3 (P

hase

2)

23

MA

R20

17

Conf

iden

tial

Pa

ge 5

2/14

9

Onc

oMed

Pha

rmac

eutic

als,

Inc.

Page

1 o

f x

59R

5-00

3 (P

hase

2)

Tab

le 1

4.1.

3.13

Bas

elin

e G

ene

Exp

ress

ion

IT

T P

opul

atio

n

Pl

aceb

o (N

=xx)

Ta

rext

umab

(N

=xx)

To

tal

(N=x

x)

Not

ch3

Expr

essi

on

n xx

xx

xx

Mea

n (S

D)

xx (x

x.x)

xx

(xx.

x)

xx (x

x.x)

Med

ian

xx

xx

xx

25

th, 7

5th P

erce

ntile

xx

, xx

xx, x

x xx

, xx

M

in, M

ax

xx, x

x xx

, xx

xx, x

x

H

es1

Expr

essi

on

n xx

xx

xx

Mea

n (S

D)

xx (x

x.x)

xx

(xx.

x)

xx (x

x.x)

Med

ian

xx

xx

xx

25

th, 7

5th P

erce

ntile

xx

, xx

xx, x

x xx

, xx

M

in, M

ax

xx, x

x xx

, xx

xx, x

x

H

ey1

Expr

essi

on

n xx

xx

xx

Mea

n (S

D)

xx (x

x.x)

xx

(xx.

x)

xx (x

x.x)

Med

ian

xx

xx

xx

25

th, 7

5th P

erce

ntile

xx

, xx

xx, x

x xx

, xx

M

in, M

ax

xx, x

x xx

, xx

xx, x

x

Prog

ram

mer

not

es: (

a) a

dd a

dditi

onal

row

s for

Hey

2 Ex

pres

sion

and

Hes

6 Ex

pres

sion

, (b)

repe

at th

is ta

ble

usin

g th

e sa

fety

and

per

-pro

toco

l pop

ulat

ions

Onc

oMed

Pha

rmac

eutic

als,

Inc.

Stat

istic

al A

naly

sis P

lan

59R

5-00

3 (P

hase

2)

23

MA

R20

17

Conf

iden

tial

Pa

ge 5

3/14

9

Onc

oMed

Pha

rmac

eutic

als,

Inc.

Page

1 o

f x

59R

5-00

3 (P

hase

2)

Tab

le 1

4.1.

3.16

Prio

r an

d C

onco

mita

nt M

edic

atio

ns

Sa

fety

Pop

ulat

ion

A

TC C

lass

[1]

Pr

efer

red

Nam

e Pl

aceb

o (N

=xx)

Ta

rext

umab

(N

=xx)

Subj

ects

Rec

eivi

ng a

ny P

rior o

r Con

com

itant

Med

icat

ions

xx

(xx.

x%)

xx (x

x.x%

)

ATC

Cla

ss 1

Pref

erre

d N

ame

1.1

xx (x

x.x%

) xx

(xx.

x%)

Pr

efer

red

Nam

e 1.

2 xx

(xx.

x%)

xx (x

x.x%

)

Pref

erre

d N

ame

1.3

xx (x

x.x%

) xx

(xx.

x%)

A

TC C

lass

2

Pr

efer

red

Nam

e 2.

1 xx

(xx.

x%)

xx (x

x.x%

)

Pref

erre

d N

ame

2.2

xx (x

x.x%

) xx

(xx.

x%)

Pr

efer

red

Nam

e 2.

3 xx

(xx.

x%)

xx (x

x.x%

)

ATC

Cla

ss 3

Pref

erre

d N

ame

3.1

xx (x

x.x%

) xx

(xx.

x%)

Pr

efer

red

Nam

e 3.

2 xx

(xx.

x%)

xx (x

x.x%

)

Pref

erre

d N

ame

3.3

xx (x

x.x%

) xx

(xx.

x%)

N

ote:

At e

ach

leve

l of s

umm

atio

n (o

vera

ll, A

TC c

lass

and

pre

ferr

ed n

ame)

, sub

ject

s rep

ortin

g m

ore

than

one

med

icat

ion

are

coun

ted

only

onc

e.

[1] A

TC C

lass

and

Pre

ferr

ed N

ame

are

code

d ac

cord

ing

to th

e W

HO

Dru

g D

ictio

nary

Enh

ance

d (v

ersi

on M

arch

1, 2

014)

.

Onc

oMed

Pha

rmac

eutic

als,

Inc.

Stat

istic

al A

naly

sis P

lan

59R

5-00

3 (P

hase

2)

23

MA

R20

17

Conf

iden

tial

Pa

ge 5

4/14

9

Onc

oMed

Pha

rmac

eutic

als,

Inc.

Page

1 o

f x

59R

5-00

3 (P

hase

2)

Tab

le 1

4.2.

1.1

O

vera

ll Su

rviv

al

IT

T P

opul

atio

n

Pl

aceb

o (N

=xx)

Ta

rext

umab

(N

=xx)

Tota

l Fol

low

-Up

Tim

e (p

erso

n-ye

ars)

[1]

xxx.

x xx

x.x

Num

ber o

f Sub

ject

s who

Die

d xx

(xx.

x%)

xx (x

x.x%

) N

umbe

r of S

ubje

cts w

ho d

id n

ot D

ie (C

enso

red)

xx

(xx.

x%)

xx (x

x.x%

)

Haz

ard

[2]

0.xx

0.

xx

K

apla

n-M

eier

Est

imat

es: Q

uarti

les [

95%

C.I.

] (d

ays)

25th

Per

cent

ile

xxx

[xxx

,xxx

] xx

x [x

xx,x

xx]

50

th P

erce

ntile

xx

x [x

xx,x

xx]

xxx

[xxx

,xxx

]

75th

Per

cent

ile

xxx

[xxx

,xxx

] xx

x [x

xx,x

xx]

K

apla

n-M

eier

Est

imat

e (#

at r

isk)

[SE]

180

Day

s 0.

xx (x

x) [x

.xx]

0.

xx (x

x) [x

.xx]

360

Day

s 0.

xx (x

x) [x

.xx]

0.

xx (x

x) [x

.xx]

540

Day

s 0.

xx (x

x) [x

.xx]

0.

xx (x

x) [x

.xx]

720

Day

s 0.

xx (x

x) [x

.xx]

0.

xx (x

x) [x

.xx]

Ran

ge (S

ubje

cts w

ho D

ied)

(day

s)

xxx,

xxx

xx

x, x

xx

Ran

ge (A

ll Su

bjec

ts) (

days

) xx

x, x

xx

xxx,

xxx

Haz

ard

Rat

io [9

5% C

.I.] [3

]

x.xx

[x.x

x,x.

xx]

P-va

lue

[3]

0.

xxx

N

ote:

Ove

rall

Surv

ival

= D

ate

of D

ocum

enta

tion

of D

eath

– R

ando

miz

atio

n D

ate

+ 1.

Sub

ject

s who

had

not

exp

erie

nced

dea

th b

y th

eir l

ast c

onta

ct d

ate

wer

e ce

nsor

ed a

t tha

t tim

e. S

ubje

cts l

acki

ng

data

afte

r ran

dom

izat

ion

who

do

not d

ie h

ave

thei

r eve

nt ti

me

cens

ored

on

the

date

of r

ando

miz

atio

n w

ith d

urat

ion

of 1

day

. For

det

aile

d ev

ent a

nd c

enso

ring

rule

s, re

fer t

o pr

otoc

ol se

ctio

n 13

.5.4

and

SA

P se

ctio

n 8.

6. C

.I. =

Con

fiden

ce In

terv

al. S

E =

Stan

dard

Erro

r. [1

] Su

m o

f all

indi

vidu

al fo

llow

-up

times

in d

ays d

ivid

ed b

y 36

5.25

. [2

] N

umbe

r of d

eath

s / to

tal f

ollo

w-u

p tim

e.

[3] H

azar

d ra

tio, 9

5% C

.I. a

nd p

-val

ue fr

om C

ox p

ropo

rtion

al h

azar

ds m

odel

with

mai

n ef

fect

s for

trea

tmen

t, pl

atin

um c

hoic

e an

d pr

ior t

reat

men

t mod

ality

.

Prog

ram

mer

not

es: (

a) re

peat

this

tabl

e us

ing

the

per-

prot

ocol

pop

ulat

ion

Onc

oMed

Pha

rmac

eutic

als,

Inc.

Stat

istic

al A

naly

sis P

lan

59R

5-00

3 (P

hase

2)

23

MA

R20

17

Conf

iden

tial

Pa

ge 5

5/14

9

Onc

oMed

Pha

rmac

eutic

als,

Inc.

Page

1 o

f x

59R

5-00

3 (P

hase

2)

Tab

le 1

4.2.

1.3

O

vera

ll Su

rviv

al fo

r Su

bjec

ts R

ecei

ving

Cis

plat

in

IT

T P

opul

atio

n

Pl

aceb

o (N

=xx)

Ta

rext

umab

(N

=xx)

Plat

inum

Cho

ice

[1]

C

ispl

atin

xx

(xx.

x%)

xx (x

x.x%

)

Car

bopl

atin

xx

(xx.

x%)

xx (x

x.x%

)

Tota

l Fol

low

-Up

Tim

e (p

erso

n-ye

ars)

[2]

xxx.

x xx

x.x

Num

ber o

f Sub

ject

s who

Die

d xx

(xx.

x%)

xx (x

x.x%

) N

umbe

r of S

ubje

cts w

ho d

id n

ot D

ie (C

enso

red)

xx

(xx.

x%)

xx (x

x.x%

)

Haz

ard

[3]

0.xx

0.

xx

K

apla

n-M

eier

Est

imat

es:

Qua

rtile

s [95

% C

.I.] (

days

)

25th

Per

cent

ile

xxx

[xxx

,xxx

] xx

x [x

xx,x

xx]

50

th P

erce

ntile

xx

x [x

xx,x

xx]

xxx

[xxx

,xxx

]

75th

Per

cent

ile

xxx

[xxx

,xxx

] xx

x [x

xx,x

xx]

K

apla

n-M

eier

Est

imat

e (#

at r

isk)

[SE]

180

Day

s 0.

xx (x

x) [x

.xx]

0.

xx (x

x) [x

.xx]

360

Day

s 0.

xx (x

x) [x

.xx]

0.

xx (x

x) [x

.xx]

40 D

ays

0.xx

(xx)

[x.x

x]

0.xx

(xx)

[x.x

x]

72

0 D

ays

0.xx

(xx)

[x.x

x]

0.xx

(xx)

[x.x

x]

R

ange

(Sub

ject

s who

Die

d) (d

ays)

xx

x, x

xx

xxx,

xxx

R

ange

(All

Subj

ects

) (da

ys)

xxx,

xxx

xx

x, x

xx

H

azar

d R

atio

[95%

C.I.

] [4]

x.

xx [x

.xx,

x.xx

] P-

valu

e [4

]

0.xx

x

Not

e: O

vera

ll Su

rviv

al =

Dat

e of

Doc

umen

tatio

n of

Dea

th –

Ran

dom

izat

ion

Dat

e +

1. S

ubje

cts w

ho h

ad n

ot e

xper

ienc

ed d

eath

by

thei

r las

t con

tact

dat

e w

ere

cens

ored

at t

hat t

ime.

Sub

ject

s lac

king

da

ta a

fter r

ando

miz

atio

n w

ho d

o no

t die

hav

e th

eir e

vent

tim

e ce

nsor

ed o

n th

e da

te o

f ran

dom

izat

ion

with

dur

atio

n of

1 d

ay. F

or d

etai

led

even

t and

cen

sorin

g ru

les,

refe

r to

prot

ocol

sect

ion

13.5

.4 a

nd

SAP

sect

ion

8.6.

C.I.

= C

onfid

ence

Inte

rval

. SE

= St

anda

rd E

rror.

[1] A

naly

ses p

rese

nted

in th

is ta

ble

incl

ude

only

subj

ects

who

rece

ived

cis

plat

in. P

erce

ntag

es b

elow

the

first

set o

f row

s are

bas

ed o

n su

bjec

ts w

ho re

ceiv

ed c

ispl

atin

. [2

] Su

m o

f all

indi

vidu

al fo

llow

-up

times

in d

ays d

ivid

ed b

y 36

5.25

. [3

] N

umbe

r of d

eath

s / to

tal f

ollo

w-u

p tim

e.

[4] H

azar

d ra

tio, 9

5% C

.I. a

nd p

-val

ue fr

om C

ox p

ropo

rtion

al h

azar

ds m

odel

with

mai

n ef

fect

s for

trea

tmen

t and

prio

r tre

atm

ent m

odal

ity.

Prog

ram

mer

not

es: (

a) re

peat

this

tabl

e us

ing

the

per-

prot

ocol

pop

ulat

ion

Onc

oMed

Pha

rmac

eutic

als,

Inc.

Stat

istic

al A

naly

sis P

lan

59R

5-00

3 (P

hase

2)

23

MA

R20

17

Conf

iden

tial

Pa

ge 5

6/14

9

Onc

oMed

Pha

rmac

eutic

als,

Inc.

Page

1 o

f x

59R

5-00

3 (P

hase

2)

Tab

le 1

4.2.

1.5

O

vera

ll Su

rviv

al fo

r Su

bjec

ts R

ecei

ving

Car

bopl

atin

ITT

Pop

ulat

ion

Pl

aceb

o (N

=xx)

Ta

rext

umab

(N

=xx)

Plat

inum

Cho

ice

[1]

C

ispl

atin

xx

(xx.

x%)

xx (x

x.x%

)

Car

bopl

atin

xx

(xx.

x%)

xx (x

x.x%

)

Tota

l Fol

low

-Up

Tim

e (p

erso

n-ye

ars)

[2]

xxx.

x xx

x.x

Num

ber o

f Sub

ject

s who

Die

d xx

(xx.

x%)

xx (x

x.x%

) N

umbe

r of S

ubje

cts w

ho d

id n

ot D

ie (C

enso

red)

xx

(xx.

x%)

xx (x

x.x%

)

Haz

ard

[3]

0.xx

0.

xx

K

apla

n-M

eier

Est

imat

es: Q

uarti

les [

95%

C.I.

] (da

ys)

25

th P

erce

ntile

xx

x [x

xx,x

xx]

xxx

[xxx

,xxx

]

50th

Per

cent

ile

xxx

[xxx

,xxx

] xx

x [x

xx,x

xx]

75

th P

erce

ntile

xx

x [x

xx,x

xx]

xxx

[xxx

,xxx

]

Kap

lan-

Mei

er E

stim

ate

(# a

t ris

k) [S

E]

18

0 D

ays

0.xx

(xx)

[x.x

x]

0.xx

(xx)

[x.x

x]

36

0 D

ays

0.xx

(xx)

[x.x

x]

0.xx

(xx)

[x.x

x]

54

0 D

ays

0.xx

(xx)

[x.x

x]

0.xx

(xx)

[x.x

x]

72

0 D

ays

0.xx

(xx)

[x.x

x]

0.xx

(xx)

[x.x

x]

R

ange

(Sub

ject

s who

Die

d) (d

ays)

xx

x, x

xx

xxx,

xxx

R

ange

(All

Subj

ects

) (da

ys)

xxx,

xxx

xx

x, x

xx

H

azar

d R

atio

[95%

C.I.

] [4]

x.

xx [x

.xx,

x.xx

] P-

valu

e [4

]

0.xx

x

Not

e: O

vera

ll Su

rviv

al =

Dat

e of

Doc

umen

tatio

n of

Dea

th –

Ran

dom

izat

ion

Dat

e +

1. S

ubje

cts w

ho h

ad n

ot e

xper

ienc

ed d

eath

by

thei

r las

t con

tact

dat

e w

ere

cens

ored

at t

hat t

ime.

Sub

ject

s lac

king

da

ta a

fter r

ando

miz

atio

n w

ho d

o no

t die

hav

e th

eir e

vent

tim

e ce

nsor

ed o

n th

e da

te o

f ran

dom

izat

ion

with

dur

atio

n of

1 d

ay. F

or d

etai

led

even

t and

cen

sorin

g ru

les,

refe

r to

prot

ocol

sect

ion

13.5

.4 a

nd

SAP

sect

ion

8.6.

C.I.

= C

onfid

ence

Inte

rval

. SE

= St

anda

rd E

rror.

[1] A

naly

ses p

rese

nted

in th

is ta

ble

incl

ude

only

subj

ects

who

rece

ived

car

bopl

atin

. Per

cent

ages

bel

ow th

e fir

st se

t of r

ows a

re b

ased

on

subj

ects

who

rece

ived

car

bopl

atin

. [2

] Su

m o

f all

indi

vidu

al fo

llow

-up

times

in d

ays d

ivid

ed b

y 36

5.25

. [3

] N

umbe

r of d

eath

s / to

tal f

ollo

w-u

p tim

e.

[4] H

azar

d ra

tio, 9

5% C

.I. a

nd p

-val

ue fr

om C

ox p

ropo

rtion

al h

azar

ds m

odel

with

mai

n ef

fect

s for

trea

tmen

t and

prio

r tre

atm

ent m

odal

ity.

Prog

ram

mer

not

es: (

a) re

peat

this

tabl

e us

ing

the

per-

prot

ocol

pop

ulat

ion

Onc

oMed

Pha

rmac

eutic

als,

Inc.

Stat

istic

al A

naly

sis P

lan

59R

5-00

3 (P

hase

2)

23

MA

R20

17

Conf

iden

tial

Pa

ge 5

7/14

9

Onc

oMed

Pha

rmac

eutic

als,

Inc.

Page

1 o

f x

59R

5-00

3 (P

hase

2)

Tab

le 1

4.2.

1.7

O

vera

ll Su

rviv

al –

Impa

ct o

f Bio

mar

ker

Exp

ress

ion

IT

T P

opul

atio

n

M

odel

Coe

ffici

ents

(SE)

[1]

H

azar

d R

atio

[95%

Con

fiden

ce In

terv

al] [1

]

Bio

mar

ker

Trea

tmen

t

Trea

tmen

t x

Bio

mar

ker

Inte

ract

ion

A

t 25th

Pe

rcen

tile

At 5

0th

Perc

entil

e A

t 75th

Pe

rcen

tile

N

otch

3 xx

.x (x

x.x)

xx

.x (x

x.x)

x.xx

[x.x

x,xx

.xx]

x.

xx [x

.xx,

xx.x

x]

x.xx

[x.x

x,xx

.xx]

H

es1

xx.x

(xx.

x)

xx.x

(xx.

x)

x.

xx [x

.xx,

xx.x

x]

x.xx

[x.x

x,xx

.xx]

x.

xx [x

.xx,

xx.x

x]

Hey

2 xx

.x (x

x.x)

xx

.x (x

x.x)

x.xx

[x.x

x,xx

.xx]

x.

xx [x

.xx,

xx.x

x]

x.xx

[x.x

x,xx

.xx]

H

ey1

xx.x

(xx.

x)

xx.x

(xx.

x)

x.

xx [x

.xx,

xx.x

x]

x.xx

[x.x

x,xx

.xx]

x.

xx [x

.xx,

xx.x

x]

Hes

6 xx

.x (x

x.x)

xx

.x (x

x.x)

x.xx

[x.x

x,xx

.xx]

x.

xx [x

.xx,

xx.x

x]

x.xx

[x.x

x,xx

.xx]

[1] C

oeffi

cien

ts, h

azar

d ra

tios a

nd 9

5% c

onfid

ence

inte

rval

s are

from

Cox

pro

porti

onal

haz

ards

mod

els w

ith e

ffec

ts fo

r tre

atm

ent,

biom

arke

r and

trea

tmen

t-by-

biom

arke

r int

erac

tion.

A se

para

te m

odel

w

as u

sed

for e

ach

biom

arke

r.

Prog

ram

mer

not

es: (

a) re

peat

this

tabl

e us

ing

the

per-

prot

ocol

pop

ulat

ion

Onc

oMed

Pha

rmac

eutic

als,

Inc.

Stat

istic

al A

naly

sis P

lan

59R

5-00

3 (P

hase

2)

23

MA

R20

17

Conf

iden

tial

Pa

ge 5

8/14

9

Onc

oMed

Pha

rmac

eutic

als,

Inc.

Page

1 o

f x

59R

5-00

3 (P

hase

2)

Tab

le 1

4.2.

1.9

O

vera

ll Su

rviv

al –

Impa

ct o

f Not

ch3

Exp

ress

ion

in S

ubje

cts w

ith H

igh/

Low

Not

ch P

athw

ay M

arke

rs

IT

T P

opul

atio

n

M

odel

Coe

ffici

ents

(SE)

[1]

H

azar

d R

atio

[95%

Con

fiden

ce In

terv

al] [1

]

Bio

mar

ker

Bio

mar

ker

Leve

l n

Trea

tmen

t Tr

eatm

ent x

N

otch

3

At N

otch

3 25

th P

erce

ntile

A

t Not

ch3

50th

Per

cent

ile

At N

otch

3 75

th P

erce

ntile

N3R

PI [2

] H

igh

xx

xx.x

(xx.

x)

xx.x

(xx.

x)

x.

xx [x

.xx,

xx.x

x]

x.xx

[x.x

x,xx

.xx]

x.

xx [x

.xx,

xx.x

x]

Lo

w

xx

xx.x

(xx.

x)

xx.x

(xx.

x)

x.

xx [x

.xx,

xx.x

x]

x.xx

[x.x

x,xx

.xx]

x.

xx [x

.xx,

xx.x

x]

H

es1

Hig

h xx

xx

.x (x

x.x)

xx

.x (x

x.x)

x.xx

[x.x

x,xx

.xx]

x.

xx [x

.xx,

xx.x

x]

x.xx

[x.x

x,xx

.xx]

Low

xx

xx

.x (x

x.x)

xx

.x (x

x.x)

x.xx

[x.x

x,xx

.xx]

x.

xx [x

.xx,

xx.x

x]

x.xx

[x.x

x,xx

.xx]

Hey

2 H

igh

xx

xx.x

(xx.

x)

xx.x

(xx.

x)

x.

xx [x

.xx,

xx.x

x]

x.xx

[x.x

x,xx

.xx]

x.

xx [x

.xx,

xx.x

x]

Lo

w

xx

xx.x

(xx.

x)

xx.x

(xx.

x)

x.

xx [x

.xx,

xx.x

x]

x.xx

[x.x

x,xx

.xx]

x.

xx [x

.xx,

xx.x

x]

H

ey1

Hig

h xx

xx

.x (x

x.x)

xx

.x (x

x.x)

x.xx

[x.x

x,xx

.xx]

x.

xx [x

.xx,

xx.x

x]

x.xx

[x.x

x,xx

.xx]

Low

xx

xx

.x (x

x.x)

xx

.x (x

x.x)

x.xx

[x.x

x,xx

.xx]

x.

xx [x

.xx,

xx.x

x]

x.xx

[x.x

x,xx

.xx]

Hes

6 H

igh

xx

xx.x

(xx.

x)

xx.x

(xx.

x)

x.

xx [x

.xx,

xx.x

x]

x.xx

[x.x

x,xx

.xx]

x.

xx [x

.xx,

xx.x

x]

Lo

w

xx

xx.x

(xx.

x)

xx.x

(xx.

x)

x.

xx [x

.xx,

xx.x

x]

x.xx

[x.x

x,xx

.xx]

x.

xx [x

.xx,

xx.x

x]

[1

] C

oeffi

cien

ts, h

azar

d ra

tios a

nd 9

5% c

onfid

ence

inte

rval

s are

from

Cox

pro

porti

onal

haz

ards

mod

els w

ith e

ffec

ts fo

r tre

atm

ent,

Not

ch3

and

treat

men

t-by-

Not

ch3

inte

ract

ion.

A se

para

te m

odel

was

us

ed fo

r eac

h bi

omar

ker.

[2] N

3RPI

is th

e N

otch

3-re

late

d PF

S In

dex;

N3R

PI =

–0.

569*

HES

6*N

OTC

H3

+1.0

76*H

ES1*

HES

6*N

OTC

H3

Prog

ram

mer

not

es: (

a) re

peat

this

tabl

e us

ing

the

per-

prot

ocol

pop

ulat

ion

Onc

oMed

Pha

rmac

eutic

als,

Inc.

Stat

istic

al A

naly

sis P

lan

59R

5-00

3 (P

hase

2)

23

MA

R20

17

Conf

iden

tial

Pa

ge 5

9/14

9

Onc

oMed

Pha

rmac

eutic

als,

Inc.

Page

1 o

f x

59R

5-00

3 (P

hase

2)

Tab

le 1

4.2.

2.1

Pr

ogre

ssio

n-Fr

ee S

urvi

val –

Pri

mar

y A

naly

sis

IT

T P

opul

atio

n

Pl

aceb

o (N

=xx)

Ta

rext

umab

(N

=xx)

Tota

l Fol

low

-Up

Tim

e (p

erso

n-ye

ars)

[1]

xxx.

x xx

x.x

Num

ber o

f Sub

ject

s with

Dis

ease

Pro

gres

sion

or D

eath

xx

(xx.

x%)

xx (x

x.x%

) N

umbe

r of S

ubje

cts w

ho d

id n

ot P

rogr

ess o

r Die

(Cen

sore

d)

xx (x

x.x%

) xx

(xx.

x%)

H

azar

d [2

] 0.

xx

0.xx

Kap

lan-

Mei

er E

stim

ates

: Qua

rtile

s [95

% C

.I.] (

days

)

25th

Per

cent

ile

xxx

[xxx

,xxx

] xx

x [x

xx,x

xx]

50

th P

erce

ntile

xx

x [x

xx,x

xx]

xxx

[xxx

,xxx

]

75th

Per

cent

ile

xxx

[xxx

,xxx

] xx

x [x

xx,x

xx]

R

ange

(Sub

ject

s who

Pro

gres

sed

or D

ied)

(day

s)

xxx,

xxx

xx

x, x

xx

Ran

ge (A

ll Su

bjec

ts) (

days

) xx

x, x

xx

xxx,

xxx

Haz

ard

Rat

io [9

5% C

.I.] [3

]

x.xx

[x.x

x,x.

xx]

P-va

lue

[4]

0.

xxx

N

ote:

PFS

= D

ate

of D

ocum

enta

tion

of D

eath

/Pro

gres

sion

– R

ando

miz

atio

n D

ate

+ 1.

Sub

ject

s who

had

not

exp

erie

nced

dea

th o

r pro

gres

sion

by

thei

r las

t con

tact

wer

e ce

nsor

ed a

t the

tim

e of

thei

r las

t ra

diog

raph

ic re

spon

se a

sses

smen

t. Su

bjec

ts la

ckin

g a

radi

ogra

phic

resp

onse

ass

essm

ent a

fter r

ando

miz

atio

n w

ho d

o no

t pro

gres

s or d

ie h

ave

thei

r eve

nt ti

me

cens

ored

on

the

date

of r

ando

miz

atio

n w

ith d

urat

ion

of 1

day

. For

det

aile

d ev

ent a

nd c

enso

ring

rule

s ref

er to

pro

toco

l sec

tion

13.5

.1 a

nd S

AP

sect

ion

8.1.

C.I.

= C

onfid

ence

Inte

rval

. [1

] Sum

of a

ll in

divi

dual

follo

w-u

p tim

es in

day

s div

ided

by

365.

25.

[2] N

umbe

r of S

ubje

cts w

ith D

isea

se P

rogr

essi

on o

r Dea

th/ T

otal

Fol

low

-up

Tim

e (P

erso

n-ye

ars)

. [3

] H

azar

d ra

tio a

nd 9

5% C

.I. fr

om C

ox p

ropo

rtion

al h

azar

ds m

odel

with

mai

n ef

fect

s for

trea

tmen

t, pl

atin

um c

hoic

e an

d pr

ior t

reat

men

t mod

ality

. [4

] P-

valu

e fo

r tre

atm

ent e

ffec

t fro

m st

ratif

ied

log

rank

test

usi

ng p

latin

um c

hoic

e an

d pr

ior t

reat

men

t mod

ality

as s

tratif

icat

ion

fact

ors.

Prog

ram

mer

not

es: (

a) re

peat

this

tabl

e us

ing

the

per-

prot

ocol

pop

ulat

ion

Onc

oMed

Pha

rmac

eutic

als,

Inc.

Stat

istic

al A

naly

sis P

lan

59R

5-00

3 (P

hase

2)

23

MA

R20

17

Conf

iden

tial

Pa

ge 6

0/14

9

Onc

oMed

Pha

rmac

eutic

als,

Inc.

Page

1 o

f x

59R

5-00

3 (P

hase

2)

Tab

le 1

4.2.

2.3

Pr

ogre

ssio

n-Fr

ee S

urvi

val D

urin

g C

ombi

natio

n C

hem

othe

rapy

ITT

Pop

ulat

ion

Pl

aceb

o (N

=xx)

Ta

rext

umab

(N

=xx)

Tota

l Fol

low

-Up

Tim

e (p

erso

n-ye

ars)

[1]

xxx.

x xx

x.x

Num

ber o

f Sub

ject

s with

Dis

ease

Pro

gres

sion

or D

eath

xx

(xx.

x%)

xx (x

x.x%

) N

umbe

r of S

ubje

cts w

ho d

id n

ot P

rogr

ess o

r Die

(Cen

sore

d) [2

] xx

(xx.

x%)

xx (x

x.x%

)

Haz

ard

[3]

0.xx

0.

xx

K

apla

n-M

eier

Est

imat

es: Q

uarti

les [

95%

C.I.

] (da

ys)

25

th P

erce

ntile

xx

x [x

xx,x

xx]

xxx

[xxx

,xxx

]

50th

Per

cent

ile

xxx

[xxx

,xxx

] xx

x [x

xx,x

xx]

75

th P

erce

ntile

xx

x [x

xx,x

xx]

xxx

[xxx

,xxx

]

Ran

ge (S

ubje

cts w

ho P

rogr

esse

d or

Die

d) (d

ays)

xx

x, x

xx

xxx,

xxx

R

ange

(All

Subj

ects

) (da

ys)

xxx,

xxx

xx

x, x

xx

H

azar

d R

atio

[95%

C.I.

] [4]

x.

xx [x

.xx,

x.xx

] P-

valu

e [5

]

0.xx

x

Not

e: P

FS=

Dat

e of

Doc

umen

tatio

n of

Dea

th/P

rogr

essi

on –

Ran

dom

izat

ion

Dat

e +

1. S

ubje

cts w

ho h

ad n

ot e

xper

ienc

ed d

eath

or p

rogr

essi

on b

y th

eir l

ast c

onta

ct w

ere

cens

ored

at t

he ti

me

of th

eir l

ast

radi

ogra

phic

resp

onse

ass

essm

ent.

Subj

ects

lack

ing

a ra

diog

raph

ic re

spon

se a

sses

smen

t afte

r ran

dom

izat

ion

who

do

not p

rogr

ess o

r die

hav

e th

eir e

vent

tim

e ce

nsor

ed o

n th

e da

te o

f ran

dom

izat

ion

with

dur

atio

n of

1 d

ay. F

or d

etai

led

even

t and

cen

sorin

g ru

les r

efer

to p

roto

col s

ectio

n 13

.5.1

and

SA

P se

ctio

n 8.

1. C

.I. =

Con

fiden

ce In

terv

al.

[1] Su

m o

f all

indi

vidu

al fo

llow

-up

times

in d

ays d

ivid

ed b

y 36

5.25

. [2

] Th

e sa

me

cens

orin

g m

echa

nism

s use

d in

the

prim

ary

anal

ysis

of P

FS w

ere

empl

oyed

her

e. A

dditi

onal

ly, f

or th

is a

naly

sis,

a su

bjec

t’s P

FS w

as c

enso

red

35 d

ays (

the

sche

dule

d tim

e fo

r 1 tr

eatm

ent

cycl

e pl

us 7

day

s) fo

llow

ing

his o

r her

last

dos

e of

eto

posi

de o

r pla

tinum

. [3

] N

umbe

r of S

ubje

cts w

ith D

isea

se P

rogr

essi

on o

r Dea

th/ T

otal

Fol

low

-up

Tim

e (P

erso

n-ye

ars)

. [4

] H

azar

d ra

tio a

nd 9

5% C

.I. fr

om C

ox p

ropo

rtion

al h

azar

ds m

odel

with

mai

n ef

fect

s for

trea

tmen

t, pl

atin

um c

hoic

e an

d pr

ior t

reat

men

t mod

ality

. [5

] P-

valu

e fo

r tre

atm

ent e

ffec

t fro

m st

ratif

ied

log

rank

test

usi

ng p

latin

um c

hoic

e an

d pr

ior t

reat

men

t mod

ality

as s

tratif

icat

ion

fact

ors.

Prog

ram

mer

not

es: (

a) re

peat

this

tabl

e us

ing

the

per-

prot

ocol

pop

ulat

ion

Onc

oMed

Pha

rmac

eutic

als,

Inc.

Stat

istic

al A

naly

sis P

lan

59R

5-00

3 (P

hase

2)

23

MA

R20

17

Conf

iden

tial

Pa

ge 6

1/14

9

Onc

oMed

Pha

rmac

eutic

als,

Inc.

Page

1 o

f x

59R

5-00

3 (P

hase

2)

Tab

le 1

4.2.

2.5

Pr

ogre

ssio

n-Fr

ee S

urvi

val –

Impa

ct o

f Bio

mar

ker

Exp

ress

ion

IT

T P

opul

atio

n

M

odel

Coe

ffici

ents

(SE)

[1]

H

azar

d R

atio

[95%

Con

fiden

ce In

terv

al] [1

]

Bio

mar

ker

Trea

tmen

t

Trea

tmen

t x

Bio

mar

ker

Inte

ract

ion

A

t 25th

Pe

rcen

tile

At 5

0th

Perc

entil

e A

t 75th

Pe

rcen

tile

N

otch

3 xx

.x (x

x.x)

xx

.x (x

x.x)

x.xx

[x.x

x,xx

.xx]

x.

xx [x

.xx,

xx.x

x]

x.xx

[x.x

x,xx

.xx]

H

es1

xx.x

(xx.

x)

xx.x

(xx.

x)

x.

xx [x

.xx,

xx.x

x]

x.xx

[x.x

x,xx

.xx]

x.

xx [x

.xx,

xx.x

x]

Hey

2 xx

.x (x

x.x)

xx

.x (x

x.x)

x.xx

[x.x

x,xx

.xx]

x.

xx [x

.xx,

xx.x

x]

x.xx

[x.x

x,xx

.xx]

H

ey1

xx.x

(xx.

x)

xx.x

(xx.

x)

x.

xx [x

.xx,

xx.x

x]

x.xx

[x.x

x,xx

.xx]

x.

xx [x

.xx,

xx.x

x]

Hes

6 xx

.x (x

x.x)

xx

.x (x

x.x)

x.xx

[x.x

x,xx

.xx]

x.

xx [x

.xx,

xx.x

x]

x.xx

[x.x

x,xx

.xx]

[1] C

oeffi

cien

ts, h

azar

d ra

tios a

nd 9

5% c

onfid

ence

inte

rval

s are

from

Cox

pro

porti

onal

haz

ards

mod

els w

ith e

ffec

ts fo

r tre

atm

ent,

biom

arke

r and

trea

tmen

t-by-

biom

arke

r int

erac

tion.

A se

para

te m

odel

w

as u

sed

for e

ach

biom

arke

r.

Prog

ram

mer

not

es: (

a) re

peat

this

tabl

e us

ing

the

per-

prot

ocol

pop

ulat

ion

Onc

oMed

Pha

rmac

eutic

als,

Inc.

Stat

istic

al A

naly

sis P

lan

59R

5-00

3 (P

hase

2)

23

MA

R20

17

Conf

iden

tial

Pa

ge 6

2/14

9

Onc

oMed

Pha

rmac

eutic

als,

Inc.

Page

1 o

f x

59R

5-00

3 (P

hase

2)

Tab

le 1

4.2.

2.7

Pr

ogre

ssio

n-Fr

ee S

urvi

val –

Impa

ct o

f Not

ch3

Exp

ress

ion

in S

ubje

cts w

ith H

igh/

Low

Not

ch P

athw

ay M

arke

rs

IT

T P

opul

atio

n

M

odel

Coe

ffici

ents

(SE)

[1]

H

azar

d R

atio

[95%

Con

fiden

ce In

terv

al] [1

]

Bio

mar

ker

Bio

mar

ker

Leve

l n

Trea

tmen

t Tr

eatm

ent x

N

otch

3

At N

otch

3 25

th P

erce

ntile

A

t Not

ch3

50th

Per

cent

ile

At N

otch

3 75

th P

erce

ntile

N3R

PI [2

] H

igh

xx

xx.x

(xx.

x)

xx.x

(xx.

x)

x.

xx [x

.xx,

xx.x

x]

x.xx

[x.x

x,xx

.xx]

x.

xx [x

.xx,

xx.x

x]

Lo

w

xx

xx.x

(xx.

x)

xx.x

(xx.

x)

x.

xx [x

.xx,

xx.x

x]

x.xx

[x.x

x,xx

.xx]

x.

xx [x

.xx,

xx.x

x]

H

es1

Hig

h xx

xx

.x (x

x.x)

xx

.x (x

x.x)

x.xx

[x.x

x,xx

.xx]

x.

xx [x

.xx,

xx.x

x]

x.xx

[x.x

x,xx

.xx]

Low

xx

xx

.x (x

x.x)

xx

.x (x

x.x)

x.xx

[x.x

x,xx

.xx]

x.

xx [x

.xx,

xx.x

x]

x.xx

[x.x

x,xx

.xx]

Hey

2 H

igh

xx

xx.x

(xx.

x)

xx.x

(xx.

x)

x.

xx [x

.xx,

xx.x

x]

x.xx

[x.x

x,xx

.xx]

x.

xx [x

.xx,

xx.x

x]

Lo

w

xx

xx.x

(xx.

x)

xx.x

(xx.

x)

x.

xx [x

.xx,

xx.x

x]

x.xx

[x.x

x,xx

.xx]

x.

xx [x

.xx,

xx.x

x]

H

ey1

Hig

h xx

xx

.x (x

x.x)

xx

.x (x

x.x)

x.xx

[x.x

x,xx

.xx]

x.

xx [x

.xx,

xx.x

x]

x.xx

[x.x

x,xx

.xx]

Low

xx

xx

.x (x

x.x)

xx

.x (x

x.x)

x.xx

[x.x

x,xx

.xx]

x.

xx [x

.xx,

xx.x

x]

x.xx

[x.x

x,xx

.xx]

Hes

6 H

igh

xx

xx.x

(xx.

x)

xx.x

(xx.

x)

x.

xx [x

.xx,

xx.x

x]

x.xx

[x.x

x,xx

.xx]

x.

xx [x

.xx,

xx.x

x]

Lo

w

xx

xx.x

(xx.

x)

xx.x

(xx.

x)

x.

xx [x

.xx,

xx.x

x]

x.xx

[x.x

x,xx

.xx]

x.

xx [x

.xx,

xx.x

x]

[1

] C

oeffi

cien

ts, h

azar

d ra

tios a

nd 9

5% c

onfid

ence

inte

rval

s are

from

Cox

pro

porti

onal

haz

ards

mod

els w

ith e

ffec

ts fo

r tre

atm

ent,

Not

ch3

and

treat

men

t-by-

Not

ch3

inte

ract

ion.

A se

para

te m

odel

was

us

ed fo

r eac

h bi

omar

ker.

[2] N

3RPI

is th

e N

otch

3-re

late

d PF

S In

dex;

N3R

PI =

–0.

569*

HES

6*N

OTC

H3

+1.0

76*H

ES1*

HES

6*N

OTC

H3

Prog

ram

mer

not

es: (

a) re

peat

this

tabl

e us

ing

the

per-

prot

ocol

pop

ulat

ion

Onc

oMed

Pha

rmac

eutic

als,

Inc.

Stat

istic

al A

naly

sis P

lan

59R

5-00

3 (P

hase

2)

23

MA

R20

17

Conf

iden

tial

Pa

ge 6

3/14

9

Onc

oMed

Pha

rmac

eutic

als,

Inc.

Page

1 o

f x

59R

5-00

3 (P

hase

2)

Tab

le 1

4.2.

2.9

Pr

ogre

ssio

n-Fr

ee S

urvi

val –

Sen

sitiv

ity A

naly

sis

Pe

r-Pr

otoc

ol P

opul

atio

n

Pl

aceb

o (N

=xx)

Ta

rext

umab

(N

=xx)

Tota

l Fol

low

-Up

Tim

e (p

erso

n-ye

ars)

[1]

xxx.

x xx

x.x

Num

ber o

f Sub

ject

s with

Dis

ease

Pro

gres

sion

or D

eath

xx

(xx.

x%)

xx (x

x.x%

) N

umbe

r of S

ubje

cts w

ho d

id n

ot P

rogr

ess o

r Die

(C

enso

red)

xx

(xx.

x%)

xx (x

x.x%

)

H

azar

d [2

] 0.

xx

0.xx

Kap

lan-

Mei

er E

stim

ates

: Qua

rtile

s [95

% C

.I.] (

days

)

25th

Per

cent

ile

xxx

[xxx

,xxx

] xx

x [x

xx,x

xx]

50

th P

erce

ntile

xx

x [x

xx,x

xx]

xxx

[xxx

,xxx

]

75th

Per

cent

ile

xxx

[xxx

,xxx

] xx

x [x

xx,x

xx]

R

ange

(Sub

ject

s who

Pro

gres

sed

or D

ied)

(day

s)

xxx,

xxx

xx

x, x

xx

Ran

ge (A

ll Su

bjec

ts) (

days

) xx

x, x

xx

xxx,

xxx

Haz

ard

Rat

io [9

5% C

.I.] [3

]

x.xx

[x.x

x,x.

xx]

P-va

lue

[4]

0.

xxx

N

ote:

PFS

= D

ate

of D

ocum

enta

tion

of D

eath

/Pro

gres

sion

– R

ando

miz

atio

n D

ate

+ 1.

Sub

ject

s who

had

not

exp

erie

nced

dea

th o

r pro

gres

sion

by

thei

r las

t con

tact

wer

e ce

nsor

ed a

t the

tim

e of

thei

r las

t ra

diog

raph

ic re

spon

se a

sses

smen

t. Su

bjec

ts la

ckin

g a

radi

ogra

phic

resp

onse

ass

essm

ent a

fter r

ando

miz

atio

n w

ho d

o no

t pro

gres

s or d

ie h

ave

thei

r eve

nt ti

me

cens

ored

on

the

date

of r

ando

miz

atio

n w

ith d

urat

ion

of 1

day

. For

det

aile

d ev

ent a

nd c

enso

ring

rule

s ref

er to

pro

toco

l sec

tion

13.5

.1 a

nd S

AP

sect

ion

8.1.

C.I.

= C

onfid

ence

Inte

rval

. [1

] Sum

of a

ll in

divi

dual

follo

w-u

p tim

es in

day

s div

ided

by

365.

25.

[2] N

umbe

r of S

ubje

cts w

ith D

isea

se P

rogr

essi

on o

r Dea

th/ T

otal

Fol

low

-up

Tim

e (P

erso

n-ye

ars)

. [3

] H

azar

d ra

tio a

nd 9

5% C

.I. fr

om C

ox p

ropo

rtion

al h

azar

ds m

odel

with

trea

tmen

t as t

he o

nly

expl

anat

ory

varia

ble.

[4

] P-

valu

e fo

r tre

atm

ent e

ffec

t fro

m u

nstra

tifie

d lo

g ra

nk te

st.

Onc

oMed

Pha

rmac

eutic

als,

Inc.

Stat

istic

al A

naly

sis P

lan

59R

5-00

3 (P

hase

2)

23

MA

R20

17

Conf

iden

tial

Pa

ge 6

4/14

9

Onc

oMed

Pha

rmac

eutic

als,

Inc.

Page

1 o

f x

59R

5-00

3 (P

hase

2)

Tab

le 1

4.2.

3.1

L

andm

ark

Surv

ival

at 1

80, 3

60, 5

40 a

nd 7

20 D

ays

IT

T P

opul

atio

n

Pl

aceb

o (N

=xx)

Ta

rext

umab

(N

=xx)

P-

Val

ue

Surv

ival

(# a

t ris

k) [S

E] [1

]

18

0 D

ays

0.xx

(xx)

[x.x

x]

0.xx

(xx)

[x.x

x]

0.xx

x

360

Day

s 0.

xx (x

x) [x

.xx]

0.

xx (x

x) [x

.xx]

0.

xxx

54

0 D

ays

0.xx

(xx)

[x.x

x]

0.xx

(xx)

[x.x

x]

0.xx

x

720

Day

s 0.

xx (x

x) [x

.xx]

0.

xx (x

x) [x

.xx]

0.

xxx

[1] La

ndm

ark

surv

ival

p-v

alue

s fro

m in

depe

nden

t Z te

sts.

Prog

ram

mer

not

es: (

a) re

peat

this

tabl

e us

ing

the

per-

prot

ocol

pop

ulat

ion

Onc

oMed

Pha

rmac

eutic

als,

Inc.

Stat

istic

al A

naly

sis P

lan

59R

5-00

3 (P

hase

2)

23

MA

R20

17

Conf

iden

tial

Pa

ge 6

5/14

9

Onc

oMed

Pha

rmac

eutic

als,

Inc.

Page

1 o

f x

59R

5-00

3 (P

hase

2)

T

able

14.

2.4.

1 Su

mm

ary

Ass

essm

ent o

f Tum

or L

engt

h (m

m)

IT

T P

opul

atio

n

Plac

ebo

(N=x

x)

Ta

rext

umab

(N

=xx)

R

esul

t

Cha

nge

from

B

asel

ine

Perc

ent

Cha

nge

R

esul

t

Cha

nge

from

B

asel

ine

Perc

ent

Cha

nge

Bas

elin

e Su

m o

f Lon

gest

Dia

met

ers (

SLD

)

n

xx

xx

Mea

n (S

D)

xx.x

(xx.

xx)

xx

.x (x

x.xx

)

95%

C.I.

[x

x.x,

xx.

x]

[x

x.x,

xx.

x]

M

edia

n xx

xx

25

th, 7

5th P

erce

ntile

xx

, xx

xx

, xx

M

in, M

ax

xx, x

x

xx, x

x

C

ycle

-3, D

ay-1

Sum

of L

onge

st D

iam

eter

s (SL

D)

n xx

xx

xx

xx

xx

xx

M

ean

(SD

) xx

.x (x

x.xx

) xx

.x (x

x.xx

) xx

.x (x

x.xx

)

xx.x

(xx.

xx)

xx.x

(xx.

xx)

xx.x

(xx.

xx)

95

% C

.I.

[xx.

x, x

x.x]

[x

x.x,

xx.

x]

[xx.

x, x

x.x]

[xx.

x, x

x.x]

[x

x.x,

xx.

x]

[xx.

x, x

x.x]

Med

ian

xx

xx

xx

xx

xx

xx

25th

, 75th

Per

cent

ile

xx, x

x xx

, xx

xx, x

x

xx, x

x xx

, xx

xx, x

x

Min

, Max

xx

, xx

xx, x

x xx

, xx

xx

, xx

xx, x

x xx

, xx

A

NC

OV

A p

-val

ues [1

,2]

0.

xxx

0.xx

x

C

ycle

-5, D

ay-1

Sum

of L

onge

st D

iam

eter

s (SL

D)

[etc

eter

a]

[⁞]

[⁞]

[⁞]

[⁞]

[⁞]

[⁞]

N

ote:

tum

or le

ngth

is c

alcu

late

d as

the

sum

of t

he lo

nges

t dia

met

ers (

SLD

) for

the

targ

et le

sion

s. SD

= S

tand

ard

Dev

iatio

n; L

S =

Leas

t Squ

ares

; SE

= St

anda

rd E

rror

; C.I.

= C

onfid

ence

Inte

rval

. [1

] The

diff

eren

ce b

etw

een

the

follo

w-u

p an

d ba

selin

e SL

D (e

.g.,

SLD

C3D

1 – S

LDba

selin

e) is

the

depe

nden

t var

iabl

e in

the

AN

CO

VA

mod

el fo

r cha

nge

from

bas

elin

e. T

reat

men

t, pl

atin

um c

hoic

e (c

ispl

atin

ver

sus c

arbo

plat

in) a

nd p

rior t

reat

men

t mod

ality

(WB

RT

or P

CI)

will

be

cate

goric

al fa

ctor

s in

the

mod

el, a

nd S

LDba

selin

e will

be

incl

uded

as a

con

tinuo

us c

ovar

iate

. [2

] The

log

of th

e ra

tio o

f fol

low

-up

to b

asel

ine

SLD

(e.g

., lo

g [S

LDC

3D1/S

LDba

selin

e]) is

the

depe

nden

t var

iabl

e in

the

AN

CO

VA

mod

el fo

r per

cent

cha

nge.

Tre

atm

ent,

plat

inum

cho

ice

and

prio

r tre

atm

ent m

odal

ity w

ill b

e ca

tego

rical

fact

ors i

n th

e m

odel

, and

log

[SLD

base

line]

will

be

incl

uded

as a

con

tinuo

us c

ovar

iate

.

Prog

ram

mer

not

es: (

a) re

peat

this

tabl

e us

ing

the

per-

prot

ocol

pop

ulat

ion

Onc

oMed

Pha

rmac

eutic

als,

Inc.

Stat

istic

al A

naly

sis P

lan

59R

5-00

3 (P

hase

2)

23

MA

R20

17

Conf

iden

tial

Pa

ge 6

6/14

9

Onc

oMed

Pha

rmac

eutic

als,

Inc.

Page

1 o

f x

59R

5-00

3 (P

hase

2)

Tab

le 1

4.2.

4.3

R

ate

of C

hang

e in

Tot

al T

umor

Len

gth

at P

rogr

essi

on

IT

T P

opul

atio

n

Pl

aceb

o (N

=xx)

Ta

rext

umab

(N

=xx)

SLD

at N

adir

n

xx

xx

M

ean

(SD

) xx

.x (x

x.xx

) xx

.x (x

x.xx

)

Med

ian

xx

xx

25

th, 7

5th P

erce

ntile

xx

, xx

xx, x

x

Min

, Max

xx

, xx

xx, x

x

SLD

at P

rogr

essi

on

n

xx

xx

M

ean

(SD

) xx

.x (x

x.xx

) xx

.x (x

x.xx

)

Med

ian

xx

xx

25

th, 7

5th P

erce

ntile

xx

, xx

xx, x

x

Min

, Max

xx

, xx

xx, x

x

Rat

e of

SLD

Cha

nge

from

Nad

ir to

Pro

gres

sion

(%/d

ay) [1

]

N

xx

xx

M

ean

(SD

) xx

.x (x

x.xx

) xx

.x (x

x.xx

)

Med

ian

xx

xx

25

th, 7

5th P

erce

ntile

xx

, xx

xx, x

x

Min

, Max

xx

, xx

xx, x

x

P-va

lue

[2]

0.

xxx

N

ote:

SLD

= S

um o

f Lon

gest

Dia

met

ers (

i.e.,

tota

l tum

or le

ngth

for t

arge

t les

ions

as d

efin

ed b

y R

ECIS

T cr

iteria

[ver

sion

1.1

]).

[1] R

ate

of C

hang

e in

SLD

at p

rogr

essi

on =

100

x (S

LD a

t Pro

gres

sion

– S

LD a

t Nad

ir) /

SLD

at N

adir

/ (nu

mbe

r of d

ays b

etw

een

nadi

r and

pro

gres

sion

). [2

] P-

valu

e fo

r tre

atm

ent e

ffec

t fro

m A

NO

VA

mod

el w

ith tr

eatm

ent,

plat

inum

cho

ice

and

prio

r tre

atm

ent m

odal

ity a

s cat

egor

ical

inde

pend

ent v

aria

bles

.

Prog

ram

mer

not

es: (

a) re

peat

this

tabl

e us

ing

the

per-

prot

ocol

pop

ulat

ion

Onc

oMed

Pha

rmac

eutic

als,

Inc.

Stat

istic

al A

naly

sis P

lan

59R

5-00

3 (P

hase

2)

23

MA

R20

17

Conf

iden

tial

Pa

ge 6

7/14

9

Onc

oMed

Pha

rmac

eutic

als,

Inc.

Page

1 o

f x

59R

5-00

3 (P

hase

2)

Tab

le 1

4.2.

4.5

R

ate

of C

hang

e fr

om T

otal

Tum

or L

engt

h at

Bas

elin

e

ITT

Pop

ulat

ion

Pl

aceb

o (N

=xx)

Ta

rext

umab

(N

=xx)

SLD

at B

asel

ine

n

xx

xx

M

ean

(SD

) xx

.x (x

x.xx

) xx

.x (x

x.xx

)

Med

ian

xx

xx

25

th, 7

5th P

erce

ntile

xx

, xx

xx, x

x

Min

, Max

xx

, xx

xx, x

x

SLD

at C

ycle

3, D

ay 1

n xx

xx

Mea

n (S

D)

xx.x

(xx.

xx)

xx.x

(xx.

xx)

M

edia

n xx

xx

25th

, 75th

Per

cent

ile

xx, x

x xx

, xx

M

in, M

ax

xx, x

x xx

, xx

R

ate

of S

LD C

hang

e fro

m B

asel

ine

to C

ycle

3, D

ay 1

Ass

essm

ent (

%/d

ay) [1

]

N

xx

xx

M

ean

(SD

) xx

.x (x

x.xx

) xx

.x (x

x.xx

)

Med

ian

xx

xx

25

th, 7

5th

Perc

entil

e xx

, xx

xx, x

x

Min

, Max

xx

, xx

xx, x

x

P-va

lue

[2]

0.

xxx

N

ote:

SLD

= S

um o

f Lon

gest

Dia

met

ers (

i.e.,

tota

l tum

or le

ngth

for t

arge

t les

ions

as d

efin

ed b

y R

ECIS

T cr

iteria

[ver

sion

1.1

]).

[1] R

ate

of C

hang

e in

SLD

from

bas

elin

e to

CxD

1 =

100

x (S

LD a

t CxD

1 –

SLD

at B

asel

ine)

/ SL

D a

t Bas

elin

e / (

num

ber o

f day

s bet

wee

n ba

selin

e an

d C

xD1

asse

ssm

ent).

[2

] P-

valu

e fo

r tre

atm

ent e

ffect

from

AN

OV

A m

odel

with

trea

tmen

t, pl

atin

um c

hoic

e an

d pr

ior t

reat

men

t mod

ality

as c

ateg

oric

al in

depe

nden

t var

iabl

es.

Prog

ram

mer

not

es: (

a) a

dd ro

ws f

or (i

) SLD

at C

ycle

5, D

ay 1

and

(ii)

Rate

of S

LD C

hang

e fro

m B

asel

ine

to C

ycle

5, D

ay 1

Asse

ssm

ent;

(b) r

epea

t thi

s tab

le u

sing

the

per-

prot

ocol

pop

ulat

ion

Onc

oMed

Pha

rmac

eutic

als,

Inc.

Stat

istic

al A

naly

sis P

lan

59R

5-00

3 (P

hase

2)

23

MA

R20

17

Conf

iden

tial

Pa

ge 6

8/14

9

Onc

oMed

Pha

rmac

eutic

als,

Inc.

Page

1 o

f x

59R

5-00

3 (P

hase

2)

Tab

le 1

4.2.

5.1

B

est O

vera

ll T

umor

Res

pons

e B

ased

on

Inve

stig

ator

Ass

essm

ent

IT

T P

opul

atio

n

Plac

ebo

(N=x

x)

Ta

rext

umab

(N=x

x)

R

espo

nse

Rat

e 95

% C

.I.[2

]

Res

pons

e R

ate

95%

C.I.

[2]

Bes

t Ove

rall

Tum

or R

espo

nse

[1]

Com

plet

e R

espo

nse

(CR

) xx

.x (x

x.x%

) [x

x.x,

xx.

x]

xx

.x (x

x.x%

) [x

x.x,

xx.

x]

Pa

rtial

Res

pons

e (P

R)

xx.x

(xx.

x%)

[xx.

x, x

x.x]

xx.x

(xx.

x%)

[xx.

x, x

x.x]

Stab

le D

isea

se (S

D)

xx.x

(xx.

x%)

[xx.

x, x

x.x]

xx.x

(xx.

x%)

[xx.

x, x

x.x]

Prog

ress

ive

Dis

ease

(PD

) xx

.x (x

x.x%

) [x

x.x,

xx.

x]

xx

.x (x

x.x%

) [x

x.x,

xx.

x]

N

ot E

valu

able

(NE)

xx

.x (x

x.x%

) [x

x.x,

xx.

x]

xx

.x (x

x.x%

) [x

x.x,

xx.

x]

N

o Po

st-B

asel

ine

Tum

or A

sses

smen

t Col

lect

ed

xx.x

(xx.

x%)

[xx.

x, x

x.x]

xx.x

(xx.

x%)

[xx.

x, x

x.x]

O

vera

ll R

espo

nse

Rat

e (C

R o

r PR)

xx

.x (x

x.x%

)

xx

.x (x

x.x%

) [x

x.x,

xx.

x]

Odd

s Rat

io (T

arex

tum

ab/P

lace

bo) [3

]

x.xx

P-va

lue

[3]

0.

xxx

[1

] Tu

mor

resp

onse

bas

ed o

n R

ECIS

T cr

iteria

(ver

sion

1.1

). [2

] Tw

o-si

ded

exac

t 95%

C.I.

. [3

] O

dds r

atio

and

p-v

alue

from

logi

stic

regr

essi

on m

odel

incl

udin

g tre

atm

ent,

plat

inum

cho

ice

and

prio

r tre

atm

ent m

odal

ity a

s ind

epen

dent

var

iabl

es.

Prog

ram

mer

not

es: (

a) re

peat

this

tabl

e us

ing

the

per-

prot

ocol

pop

ulat

ion

Onc

oMed

Pha

rmac

eutic

als,

Inc.

Stat

istic

al A

naly

sis P

lan

59R

5-00

3 (P

hase

2)

23

MA

R20

17

Conf

iden

tial

Pa

ge 6

9/14

9

Onc

oMed

Pha

rmac

eutic

als,

Inc.

Page

1 o

f x

59R

5-00

3 (P

hase

2)

Tab

le 1

4.2.

5.3

B

est O

vera

ll T

umor

Res

pons

e B

ased

on

Inve

stig

ator

Ass

essm

ent –

Impa

ct o

f Bio

mar

ker

Exp

ress

ion

IT

T P

opul

atio

n

M

odel

Coe

ffici

ents

(SE)

[1]

O

dds R

atio

[95%

Con

fiden

ce In

terv

al] [1

]

Bio

mar

ker

Trea

tmen

t

Trea

tmen

t x

Bio

mar

ker

Inte

ract

ion

A

t 25th

Pe

rcen

tile

At 5

0th

Perc

entil

e A

t 75th

Pe

rcen

tile

N

otch

3 xx

.x (x

x.x)

xx

.x (x

x.x)

x.xx

[x.x

x,xx

.xx]

x.

xx [x

.xx,

xx.x

x]

x.xx

[x.x

x,xx

.xx]

H

es1

xx.x

(xx.

x)

xx.x

(xx.

x)

x.

xx [x

.xx,

xx.x

x]

x.xx

[x.x

x,xx

.xx]

x.

xx [x

.xx,

xx.x

x]

Hey

2 xx

.x (x

x.x)

xx

.x (x

x.x)

x.xx

[x.x

x,xx

.xx]

x.

xx [x

.xx,

xx.x

x]

x.xx

[x.x

x,xx

.xx]

H

ey1

xx.x

(xx.

x)

xx.x

(xx.

x)

x.

xx [x

.xx,

xx.x

x]

x.xx

[x.x

x,xx

.xx]

x.

xx [x

.xx,

xx.x

x]

Hes

6 xx

.x (x

x.x)

xx

.x (x

x.x)

x.xx

[x.x

x,xx

.xx]

x.

xx [x

.xx,

xx.x

x]

x.xx

[x.x

x,xx

.xx]

[1] C

oeffi

cien

ts, o

dds r

atio

and

95%

con

fiden

ce in

terv

al fr

om lo

gist

ic re

gres

sion

mod

els w

ith e

ffect

s for

trea

tmen

t, bi

omar

ker a

nd tr

eatm

ent-b

y-bi

omar

ker i

nter

actio

n. A

sepa

rate

mod

el w

as u

sed

for

each

bio

mar

ker.

Prog

ram

mer

not

es: (

a) re

peat

this

tabl

e us

ing

the

per-

prot

ocol

pop

ulat

ion

Onc

oMed

Pha

rmac

eutic

als,

Inc.

Stat

istic

al A

naly

sis P

lan

59R

5-00

3 (P

hase

2)

23

MA

R20

17

Conf

iden

tial

Pa

ge 7

0/14

9

Onc

oMed

Pha

rmac

eutic

als,

Inc.

Page

1 o

f x

59R

5-00

3 (P

hase

2)

Tab

le 1

4.2.

6.1

D

urat

ion

of R

espo

nse

IT

T P

opul

atio

n

Pl

aceb

o (N

=xx)

Ta

rext

umab

(N

=xx)

Num

ber o

f Sub

ject

s with

Obj

ectiv

e R

espo

nse

(CR

or P

R)

xx

xx

Tota

l Fol

low

-Up

Tim

e (p

erso

n-ye

ars)

[11]

xx

x.x

xxx.

x N

umbe

r of R

espo

nder

s with

Dis

ease

Pro

gres

sion

or D

eath

xx

(xx.

x%)

xx (x

x.x%

) N

umbe

r of R

espo

nder

s who

did

not

Pro

gres

s or D

ie (C

enso

red)

xx

(xx.

x%)

xx (x

x.x%

)

Haz

ard

[2]

0.xx

0.

xx

K

apla

n-M

eier

Est

imat

es: Q

uarti

les [

95%

C.I.

] (da

ys)

25

th P

erce

ntile

xx

x [x

xx,x

xx]

xxx

[xxx

,xxx

]

50th

Per

cent

ile

xxx

[xxx

,xxx

] xx

x [x

xx,x

xx]

75

th P

erce

ntile

xx

x [x

xx,x

xx]

xxx

[xxx

,xxx

]

Ran

ge (R

espo

nder

s who

Pro

gres

sed

or D

ied)

(day

s)

xx.x

– x

x.x

xx.x

– x

x.x

Ran

ge (A

ll R

espo

nder

s) (d

ays)

xx

.x –

xx.

x xx

.x –

xx.

x

Haz

ard

Rat

io [9

5% C

.I.] [3

]

x.xx

[x.x

x,x.

xx]

P-va

lue

[2]

0.

xxx

N

ote:

For

this

tabl

e su

mm

ary,

Res

pond

ers a

re th

ose

subj

ects

who

exp

erie

nced

an

Obj

ectiv

e R

espo

nse.

N

ote:

Ana

lyse

s pre

sent

ed in

this

tabl

e in

clud

e on

ly su

bjec

ts w

ho a

chie

ved

a C

R o

r PR.

Per

cent

ages

bel

ow th

e fir

st ro

w a

re b

ased

on

subj

ects

who

ach

ieve

d a

CR

or P

R.

Not

e: D

urat

ion

of R

espo

nse

= D

ate

of D

ocum

enta

tion

of D

eath

/Pro

gres

sion

– D

ate

of F

irst P

artia

l (PR

) or C

ompl

ete

Res

pons

e (C

R) +

1. R

espo

nder

s who

had

not

exp

erie

nced

dea

th o

r pro

gres

sion

by

thei

r las

t con

tact

wer

e ce

nsor

ed a

t the

tim

e of

thei

r las

t rad

iogr

aphi

c re

spon

se a

sses

smen

t. R

espo

nder

s lac

king

a ra

diog

raph

ic re

spon

se a

sses

smen

t afte

r firs

t res

pons

e w

ho d

o no

t pro

gres

s or d

ie h

ave

thei

r eve

nt ti

me

cens

ored

on

the

date

of f

irst r

espo

nse

with

dur

atio

n of

1 d

ay. F

or d

etai

led

even

t and

cen

sorin

g ru

les r

efer

to p

roto

col s

ectio

n 13

.5.3

and

SA

P se

ctio

n 8.

4. C

.I. =

Con

fiden

ce In

terv

al.

[1] Su

m o

f all

indi

vidu

al fo

llow

-up

times

in d

ays d

ivid

ed b

y 36

5.25

. [2

] N

umbe

r of S

ubje

cts w

ith D

isea

se P

rogr

essi

on o

r Dea

th/ T

otal

Fol

low

-up

Tim

e (P

erso

n-ye

ars)

. [3

] H

azar

d ra

tio, 9

5% C

.I. a

nd p

-val

ue fr

om C

ox p

ropo

rtion

al h

azar

ds m

odel

with

mai

n ef

fect

s for

trea

tmen

t, pl

atin

um c

hoic

e an

d pr

ior t

reat

men

t mod

ality

.

Prog

ram

mer

not

es: P

erce

ntag

es d

ispl

ayed

to b

e ba

sed

on n

umbe

r of s

ubje

cts w

ith a

n ob

ject

ive

resp

onse

.

Prog

ram

mer

not

es: (

a) re

peat

this

tabl

e us

ing

the

per-

prot

ocol

pop

ulat

ion

Onc

oMed

Pha

rmac

eutic

als,

Inc.

Stat

istic

al A

naly

sis P

lan

59R

5-00

3 (P

hase

2)

23

MA

R20

17

Conf

iden

tial

Pa

ge 7

1/14

9

Onc

oMed

Pha

rmac

eutic

als,

Inc.

Page

1 o

f x

59R

5-00

3 (P

hase

2)

Tab

le 1

4.2.

7.1

Si

tes o

f Pro

gres

sion

ITT

Pop

ulat

ion

Pl

aceb

o (N

=xx)

Ta

rext

umab

(N

=xx)

Subj

ects

with

Pro

gres

sive

Dis

ease

[1]

xx (x

x.x%

) xx

(xx.

x%)

Pr

ogre

ssio

n ba

sed

on…

New

Les

ion

xx (x

x.x%

) xx

(xx.

x%)

Ex

istin

g Le

sion

xx

(xx.

x%)

xx (x

x.x%

)

Chi

-Squ

are

p-va

lue

[2]

0.

xxx

Si

te o

f Pro

gres

sion

Prog

ress

ion

of e

xist

ing

lesi

on

xx (x

x.x%

) xx

(xx.

x%)

Li

ver

xx (x

x.x%

) xx

(xx.

x%)

Lu

ng

xx (x

x.x%

) xx

(xx.

x%)

Ly

mph

Nod

e xx

(xx.

x%)

xx (x

x.x%

)

[…]

[⁞]

[⁞]

M

ore

than

one

new

lesi

on

xx (x

x.x%

) xx

(xx.

x%)

C

hi-S

quar

e p-

valu

e [3

]

0.xx

x

[1] A

naly

ses p

rese

nted

in th

is ta

ble

incl

ude

only

subj

ects

who

had

pro

gres

sive

dis

ease

dur

ing

the

study

. Per

cent

ages

bel

ow th

e fir

st ro

w a

re b

ased

on

subj

ects

who

had

pro

gres

sive

dis

ease

on

stud

y.

[2] H

ypot

hesi

s 1 is

equ

ival

ent d

istri

butio

ns o

f man

ner o

f dis

ease

pro

gres

sion

(new

lesi

on o

r pro

gres

sion

of e

xist

ing

lesi

on).

[3] H

ypot

hesi

s 2 is

equ

ival

ent d

istri

butio

ns o

f site

of p

rogr

essi

on w

ith p

rogr

essi

on o

f an

exis

ting

lesi

on g

roup

ed in

a si

ngle

cat

egor

y (i.

e., r

egar

dles

s of s

ite).

Prog

ram

mer

not

es: (

a) re

peat

this

tabl

e us

ing

the

per-

prot

ocol

pop

ulat

ion

Onc

oMed

Pha

rmac

eutic

als,

Inc.

Stat

istic

al A

naly

sis P

lan

59R

5-00

3 (P

hase

2)

23

MA

R20

17

Conf

iden

tial

Pa

ge 7

2/14

9

Onc

oMed

Pha

rmac

eutic

als,

Inc.

Page

1 o

f x

59R

5-00

3 (P

hase

2)

Tab

le 1

4.3.

1.1

O

vera

ll Su

mm

ary

of T

reat

men

t-E

mer

gent

Adv

erse

Eve

nts (

TE

AE

s)

Sa

fety

Pop

ulat

ion

Pl

aceb

o (N

=xx)

Ta

rext

umab

(N

=xx)

Subj

ects

Rep

ortin

g at

Lea

st O

ne T

EAE

xx (x

x.x%

) xx

(xx.

x%)

Su

bjec

ts R

epor

ting

at L

east

One

TEA

E xx

(xx.

x%)

xx (x

x.x%

) Su

bjec

ts R

epor

ting

at L

east

One

TEA

E R

elat

ed to

Stu

dy D

rug

[1]

xx (x

x.x%

) xx

(xx.

x%)

Subj

ects

Rep

ortin

g at

Lea

st O

ne T

EAE

Rel

ated

to E

topo

side

xx

(xx.

x%)

xx (x

x.x%

) Su

bjec

ts R

epor

ting

at L

east

One

TEA

E R

elat

ed to

Pla

tinum

The

rapy

xx

(xx.

x%)

xx (x

x.x%

)

Subj

ects

Rep

ortin

g at

Lea

st O

ne S

erio

us T

EAE

xx (x

x.x%

) xx

(xx.

x%)

Subj

ects

Rep

ortin

g at

Lea

st O

ne S

erio

us T

EAE

Rel

ated

to S

tudy

Dru

g [1

] xx

(xx.

x%)

xx (x

x.x%

) Su

bjec

ts R

epor

ting

at L

east

One

Ser

ious

TEA

E R

elat

ed to

Eto

posid

e xx

(xx.

x%)

xx (x

x.x%

) Su

bjec

ts R

epor

ting

at L

east

One

Ser

ious

TEA

E R

elat

ed to

Pla

tinum

The

rapy

xx

(xx.

x%)

xx (x

x.x%

)

Subj

ects

Rep

ortin

g at

Lea

st O

ne G

rade

3 o

r Hig

her T

EAE

xx (x

x.x%

) xx

(xx.

x%)

Subj

ects

Rep

ortin

g at

Lea

st O

ne G

rade

4 o

r Hig

her T

EAE

xx (x

x.x%

) xx

(xx.

x%)

Su

bjec

ts R

epor

ting

TEA

E Le

adin

g to

Del

ay/In

terr

uptio

n of

Stu

dy D

rug

[1]

xx (x

x.x%

) xx

(xx.

x%)

Subj

ects

Rep

ortin

g TE

AE

Lead

ing

to D

elay

/Inte

rrup

tion

of E

topo

side

xx (x

x.x%

) xx

(xx.

x%)

Subj

ects

Rep

ortin

g TE

AE

Lead

ing

to D

elay

/Inte

rrup

tion

of P

latin

um T

hera

py

xx (x

x.x%

) xx

(xx.

x%)

Su

bjec

ts R

epor

ting

TEA

E Le

adin

g to

Dos

e R

educ

tion

of S

tudy

Dru

g [1

] xx

(xx.

x%)

xx (x

x.x%

) Su

bjec

ts R

epor

ting

TEA

E Le

adin

g to

Dos

e R

educ

tion

of E

topo

side

xx (x

x.x%

) xx

(xx.

x%)

Subj

ects

Rep

ortin

g TE

AE

Lead

ing

to D

ose

Red

uctio

n of

Pla

tinum

The

rapy

xx

(xx.

x%)

xx (x

x.x%

)

Subj

ects

Rep

ortin

g TE

AE

Lead

ing

to W

ithdr

awal

of S

tudy

Dru

g [1

] xx

(xx.

x%)

xx (x

x.x%

) Su

bjec

ts R

epor

ting

TEA

E Le

adin

g to

With

draw

al o

f Eto

posid

e xx

(xx.

x%)

xx (x

x.x%

) Su

bjec

ts R

epor

ting

TEA

E Le

adin

g to

With

draw

al o

f Pla

tinum

The

rapy

xx

(xx.

x%)

xx (x

x.x%

)

Subj

ects

Rep

ortin

g TE

AE

with

Out

com

e of

Dea

th

xx (x

x.x%

) xx

(xx.

x%)

M

axim

um C

TCA

E Se

verit

y G

rade

[2]

G

rade

1

xx (x

x.x%

) xx

(xx.

x%)

G

rade

2

xx (x

x.x%

) xx

(xx.

x%)

G

rade

3

xx (x

x.x%

) xx

(xx.

x%)

G

rade

4

xx (x

x.x%

) xx

(xx.

x%)

G

rade

5

xx (x

x.x%

) xx

(xx.

x%)

[1

] St

udy

drug

= ta

rext

umab

or p

lace

bo.

[2] C

TCA

E =

Com

mon

Ter

min

olog

y C

riter

ia fo

r Adv

erse

Eve

nts (

vers

ion

4.02

). Su

bjec

ts w

ith m

ore

than

one

TEA

E ar

e co

unte

d on

ly o

nce

at th

e hi

ghes

t CTC

AE

seve

rity

grad

e ac

ross

all

TEA

Es.

Onc

oMed

Pha

rmac

eutic

als,

Inc.

Stat

istic

al A

naly

sis P

lan

59R

5-00

3 (P

hase

2)

23

MA

R20

17

Conf

iden

tial

Pa

ge 7

3/14

9

Onc

oMed

Pha

rmac

eutic

als,

Inc.

Page

1 o

f x

59R

5-00

3 (P

hase

2)

Tab

le 1

4.3.

1.2

T

reat

men

t-E

mer

gent

Adv

erse

Eve

nts (

TE

AE

s) b

y Sy

stem

Org

an C

lass

and

Pre

ferr

ed T

erm

Safe

ty P

opul

atio

n

Syst

em O

rgan

Cla

ss /

Pr

efer

red

Term

Pl

aceb

o (N

=xx)

Ta

rext

umab

(N

=xx)

Subj

ects

Rep

ortin

g at

Lea

st O

ne Q

ualif

ying

TEA

E

xx (x

x.x%

) xx

(xx.

x%)

Sy

stem

Org

an C

lass

1

xx (x

x.x%

) xx

(xx.

x%)

Pr

efer

red

Term

1.1

xx

(xx.

x%)

xx (x

x.x%

)

Pref

erre

d Te

rm 1

.2

xx (x

x.x%

) xx

(xx.

x%)

Pr

efer

red

Term

1.3

xx

(xx.

x%)

xx (x

x.x%

)

[etc

eter

a]

[⁞]

[⁞]

Sy

stem

Org

an C

lass

2

xx (x

x.x%

) xx

(xx.

x%)

Pr

efer

red

Term

2.1

xx

(xx.

x%)

xx (x

x.x%

)

Pref

erre

d Te

rm 2

.2

xx (x

x.x%

) xx

(xx.

x%)

Pr

efer

red

Term

2.3

xx

(xx.

x%)

xx (x

x.x%

)

[etc

eter

a]

[⁞]

[⁞]

N

ote:

At e

ach

leve

l of s

umm

atio

n (o

vera

ll, sy

stem

org

an c

lass

, pre

ferr

ed te

rm),

subj

ects

repo

rting

mor

e th

an o

ne a

dver

se e

vent

are

cou

nted

onl

y on

ce.

Prog

ram

mer

not

es: (

a) p

rim

ary

sort

ord

er is

des

cend

ing

SOC

freq

uenc

y un

der t

arex

tum

ab, s

econ

dary

sort

ord

er is

des

cend

ing

PT fr

eque

ncy

unde

r tar

extu

mab

; (b)

dup

licat

e th

is ta

ble

for t

he

follo

wing

TEA

E su

bset

s mak

ing

the

nece

ssar

y ch

ange

s to

the

tabl

e’s t

itle

– (i)

TEA

Es re

late

d to

stud

y dr

ug, (

ii) T

EAEs

rela

ted

to e

topo

side

, (iii

) TEA

Es re

late

d to

pla

tinum

ther

apy,

(iv)

seri

ous

TEAE

s, (v

) ser

ious

TEA

Es re

late

d to

stud

y dr

ug, (

vi) s

erio

us T

EAEs

rela

ted

to e

topo

side,

(vii)

seri

ous T

EAEs

rela

ted

to p

latin

um th

erap

y, (v

iii) T

EAEs

lead

ing

to d

elay

/inte

rrup

tion

of st

udy

drug

, (ix

) TE

AEs l

eadi

ng to

del

ay/in

terr

uptio

n of

eto

posi

de, (

x) T

EAEs

lead

ing

to d

elay

/inte

rrup

tion

of p

latin

um th

erap

y, (x

i) TE

AEs l

eadi

ng to

dos

e re

duct

ion

of st

udy

drug

, (xi

i) TE

AEs l

eadi

ng to

dos

e re

duct

ion

of e

topo

side,

(xiii

) TEA

Es le

adin

g to

dos

e re

duct

ion

of p

latin

um th

erap

y, (x

iv) T

EAEs

lead

ing

to w

ithdr

awal

of s

tudy

dru

g, (x

v) T

EAEs

lead

ing

to w

ithdr

awal

of e

topo

side,

(xvi

) TEA

Es

lead

ing

to w

ithdr

awal

of p

latin

um th

erap

y, (x

vii)

TEAE

s lea

ding

to d

isco

ntin

uatio

n of

stud

y dr

ug, (

xviii

) TEA

Es w

ith o

utco

me

of d

eath

Onc

oMed

Pha

rmac

eutic

als,

Inc.

Stat

istic

al A

naly

sis P

lan

59R

5-00

3 (P

hase

2)

23

MA

R20

17

Conf

iden

tial

Pa

ge 7

4/14

9

Onc

oMed

Pha

rmac

eutic

als,

Inc.

Page

1 o

f x

59R

5-00

3 (P

hase

2)

Tab

le 1

4.3.

1.6

T

reat

men

t-E

mer

gent

Adv

erse

Eve

nts b

y Sy

stem

Org

an C

lass

, Pre

ferr

ed T

erm

and

CT

CA

E S

ever

ity G

rade

Safe

ty P

opul

atio

n Sy

stem

Org

an C

lass

/

Pr

efer

red

Term

Plac

ebo

(N=

)

Tare

xtum

ab

(N=

)

Gra

de 1

G

rade

2

Gra

de 3

G

rade

4

Gra

de 5

To

tal

G

rade

1

Gra

de 2

G

rade

3

Gra

de 4

G

rade

5

Tota

l

Su

bjec

ts R

epor

ting

at L

east

One

Qua

lifyi

ng T

EAE

n (%

) n

(%)

n (%

) n

(%)

n (%

) n

(%)

n

(%)

n (%

) n

(%)

n (%

) n

(%)

n (%

)

Sy

stem

Org

an C

lass

1

n (%

) n

(%)

n (%

) n

(%)

n (%

) n

(%)

n

(%)

n (%

) n

(%)

n (%

) n

(%)

n (%

) Pr

efer

red

Term

1

n (%

) n

(%)

n (%

) n

(%)

n (%

) n

(%)

n

(%)

n (%

) n

(%)

n (%

) n

(%)

n (%

) Pr

efer

red

Term

2

n (%

) n

(%)

n (%

) n

(%)

n (%

) n

(%)

n

(%)

n (%

) n

(%)

n (%

) n

(%)

n (%

) .

.

Sy

stem

Org

an C

lass

2

n (%

) n

(%)

n (%

) n

(%)

n (%

) n

(%)

n

(%)

n (%

) n

(%)

n (%

) n

(%)

n (%

) Pr

efer

red

Term

1

n (%

) n

(%)

n (%

) n

(%)

n (%

) n

(%)

n

(%)

n (%

) n

(%)

n (%

) n

(%)

n (%

) Pr

efer

red

Term

2

n (%

) n

(%)

n (%

) n

(%)

n (%

) n

(%)

n

(%)

n (%

) n

(%)

n (%

) n

(%)

n (%

) .

.

N

ote:

Gra

de 1

= M

ild; G

rade

2 =

Mod

erat

e; G

rade

3 =

Sev

ere;

Gra

de 4

= L

ife T

hrea

teni

ng; G

rade

5 =

Fat

al.

At e

ach

leve

l of s

umm

atio

n (o

vera

ll, sy

stem

org

an c

lass

, and

pre

ferr

ed te

rm),

subj

ects

repo

rting

mor

e th

an o

ne q

ualif

ying

eve

nt a

re c

ount

ed o

nly

once

at t

he h

ighe

st C

TCA

E se

verit

y gr

ade.

Prog

ram

mer

not

es: (

a) p

rim

ary

sort

ord

er is

des

cend

ing

SOC

freq

uenc

y un

der t

arex

tum

ab, s

econ

dary

sort

ord

er is

des

cend

ing

PT (t

otal

) fre

quen

cy u

nder

tare

xtum

ab (t

otal

freq

uenc

y [i.

e., s

um o

f fr

eque

ncie

s for

gra

des 1

thro

ugh

5] e

ven

thou

gh to

tal f

requ

ency

is n

ot d

ispl

ayed

in ta

ble)

; (b)

dup

licat

e th

is ta

ble

for t

he fo

llow

ing

TEAE

subs

ets m

akin

g th

e ne

cess

ary

chan

ges t

o th

e ta

ble’

s titl

e –

(i)

TEAE

s rel

ated

to st

udy

drug

, (ii)

TEA

Es re

late

d to

eto

posi

de, (

iii) T

EAEs

rela

ted

to p

latin

um th

erap

y, (i

v) se

riou

s TEA

Es, (

v) se

riou

s TEA

Es re

late

d to

stu

dy d

rug,

(vi)

seri

ous T

EAEs

rela

ted

to

etop

osid

e, (v

ii) se

riou

s TEA

Es re

late

d to

pla

tinum

ther

apy

Onc

oMed

Pha

rmac

eutic

als,

Inc.

Stat

istic

al A

naly

sis P

lan

59R

5-00

3 (P

hase

2)

23

MA

R20

17

Conf

iden

tial

Pa

ge 7

5/14

9

Onc

oMed

Pha

rmac

eutic

als,

Inc.

Page

1 o

f x

59R

5-00

3 (P

hase

2)

Tab

le 1

4.3.

1.10

Tre

atm

ent-

Em

erge

nt A

dver

se E

vent

s by

Pref

erre

d T

erm

Safe

ty P

opul

atio

n

Pref

erre

d Te

rm

Plac

ebo

(N=x

x)

Tare

xtum

ab

(N=x

x)

Su

bjec

ts R

epor

ting

at L

east

One

Qua

lifyi

ng T

EAE

xx (x

x.x%

) xx

(xx.

x%)

Pr

efer

red

Term

1

xx (x

x.x%

) xx

(xx.

x%)

Pref

erre

d Te

rm 2

xx

(xx.

x%)

xx (x

x.x%

) Pr

efer

red

Term

3

xx (x

x.x%

) xx

(xx.

x%)

Pref

erre

d Te

rm 4

xx

(xx.

x%)

xx (x

x.x%

) Pr

efer

red

Term

5

xx (x

x.x%

) xx

(xx.

x%)

Pref

erre

d Te

rm 6

xx

(xx.

x%)

xx (x

x.x%

) [e

tcet

era]

[⁞]

[⁞]

Not

e: A

t eac

h le

vel o

f sum

mat

ion

(ove

rall

and

pref

erre

d te

rm),

subj

ects

repo

rting

mor

e th

an o

ne q

ualif

ying

eve

nt a

re c

ount

ed o

nly

once

.

Prog

ram

mer

not

es: (

a) p

rim

ary

sort

ord

er is

des

cend

ing

PT fr

eque

ncy

unde

r tar

extu

mab

; (b)

dup

licat

e th

is ta

ble

for t

he fo

llow

ing

TEAE

subs

ets m

akin

g th

e ne

cess

ary

chan

ges t

o th

e ta

ble’

s titl

e –

(i)

TEAE

s rel

ated

to st

udy

drug

, (ii)

TEA

Es re

late

d to

eto

posi

de, (

iii) T

EAEs

rela

ted

to p

latin

um th

erap

y, (i

v) se

riou

s TEA

Es, (

v) se

riou

s TEA

Es re

late

d to

stud

y dr

ug, (

vi) s

erio

us T

EAEs

rela

ted

to

etop

osid

e, (v

ii) se

riou

s TEA

Es re

late

d to

pla

tinum

ther

apy,

(viii

) TEA

Es le

adin

g to

del

ay/in

terr

uptio

n of

stud

y dr

ug, (

ix) T

EAE

s lea

ding

to d

elay

/inte

rrup

tion

of e

topo

side,

(x) T

EAEs

lead

ing

to

dela

y/in

terr

uptio

n of

pla

tinum

ther

apy,

(xi)

TEAE

s lea

ding

to d

ose

redu

ctio

n of

stud

y dr

ug, (

xii)

TEAE

s lea

ding

to d

ose

redu

ctio

n of

eto

posid

e, (x

iii) T

EAEs

lead

ing

to d

ose

redu

ctio

n of

pla

tinum

th

erap

y, (x

iv) T

EAEs

lead

ing

to w

ithdr

awal

of s

tudy

dru

g, (x

v) T

EAEs

lead

ing

to w

ithdr

awal

of e

topo

side

, (xv

i) TE

AEs l

eadi

ng to

with

draw

al o

f pla

tinum

ther

apy,

(xvi

i) TE

AEs

lead

ing

to d

isco

ntin

uatio

n of

stud

y dr

ug, (

xviii

) TEA

Es w

ith o

utco

me

of d

eath

Onc

oMed

Pha

rmac

eutic

als,

Inc.

Stat

istic

al A

naly

sis P

lan

59R

5-00

3 (P

hase

2)

23

MA

R20

17

Conf

iden

tial

Pa

ge 7

6/14

9

Onc

oMed

Pha

rmac

eutic

als,

Inc.

Page

1 o

f x

59R

5-00

3 (P

hase

2)

Tab

le 1

4.3.

4.1

H

emat

olog

y

Safe

ty P

opul

atio

n

Plac

ebo

(N=x

x)

Ta

rext

umab

(N

=xx)

Labo

rato

ry P

aram

eter

Ti

me

Poin

t R

esul

t C

hang

e fro

m

Bas

elin

e

Res

ult

Cha

nge

from

B

asel

ine

H

emog

lobi

n (g

/dL)

B

asel

ine

[1]

n

xx

xx

M

ean

(SD

) xx

.x (x

x.xx

)

xx

.x (x

x.xx

)

Med

ian

xx

xx

25

th, 7

5th P

erce

ntile

xx

, xx

xx, x

x

Min

, Max

xx

, xx

xx, x

x

Max

imum

Pos

t-Bas

elin

e

n xx

xx

xx

xx

Mea

n (S

D)

xx.x

(xx.

xx)

xx.x

(xx.

xx)

xx

.x (x

x.xx

) xx

.x (x

x.xx

)

M

edia

n xx

xx

xx

xx

25th

, 75th

Per

cent

ile

xx, x

x xx

, xx

xx

, xx

xx, x

x

M

in, M

ax

xx, x

x xx

, xx

xx

, xx

xx, x

x

M

inim

um P

ost-B

asel

ine

n

xx

xx

xx

xx

M

ean

(SD

) xx

.x (x

x.xx

) xx

.x (x

x.xx

)

xx.x

(xx.

xx)

xx.x

(xx.

xx)

Med

ian

xx

xx

xx

xx

25

th, 7

5th P

erce

ntile

xx

, xx

xx, x

x

xx, x

x xx

, xx

Min

, Max

xx

, xx

xx, x

x

xx, x

x xx

, xx

Last

Obs

erva

tion

Post

-Bas

elin

e

n xx

xx

xx

xx

Mea

n (S

D)

xx.x

(xx.

xx)

xx.x

(xx.

xx)

xx

.x (x

x.xx

) xx

.x (x

x.xx

)

M

edia

n xx

xx

xx

xx

25th

, 75th

Perc

entil

e xx

, xx

xx, x

x

xx, x

x xx

, xx

Min

, Max

xx

, xx

xx, x

x

xx, x

x xx

, xx

H

emat

ocrit

(%)

Bas

elin

e [1

]

[etc

eter

a]

[⁞]

[⁞]

[⁞]

[⁞]

[⁞]

[1

] B

asel

ine

is d

efin

ed a

s the

last

non

-mis

sing

val

ue p

rior t

o fir

st d

ose

of st

udy

drug

.

Prog

ram

mer

not

es: (

a) c

ontin

ue fo

r all

rem

aini

ng h

emat

olog

y pa

ram

eter

s; (b

) dup

licat

e ta

ble

for (

i) se

rum

che

mis

try,

(ii)

coag

ulat

ion

test

s (PT

, aPT

T an

d IN

R)

Onc

oMed

Pha

rmac

eutic

als,

Inc.

Stat

istic

al A

naly

sis P

lan

59R

5-00

3 (P

hase

2)

23

MA

R20

17

Conf

iden

tial

Pa

ge 7

7/14

9

Onc

oMed

Pha

rmac

eutic

als,

Inc.

Page

1 o

f x

59R

5-00

3 (P

hase

2)

Tab

le 1

4.3.

4.2

H

emat

olog

y –

Shift

from

Bas

elin

e

Safe

ty P

opul

atio

n

Labo

rato

ry P

aram

eter

Shift

from

Bas

elin

e [1

] P

lace

bo

(N=

)

Tare

xtum

ab

(N=

)

Hem

oglo

bin

(g/d

L)

Low

or N

orm

al to

Any

Hig

h Po

st-B

asel

ine

n (%

) n

(%)

N

orm

al o

r Hig

h to

Any

Low

Pos

t-Bas

elin

e n

(%)

n (%

)

Low

or N

orm

al to

Las

t Obs

erva

tion

Hig

h Po

st-B

asel

ine

n (%

) n

(%)

N

orm

al o

r Hig

h to

Las

t Obs

erva

tion

Low

Pos

t-Bas

elin

e n

(%)

n (%

)

H

emat

ocrit

(%)

…

.

[1] B

asel

ine

is d

efin

ed a

s the

last

non

-mis

sing

val

ue p

rior t

o fir

st d

ose

of st

udy

drug

.

Prog

ram

mer

not

es: (

a) c

ontin

ue fo

r all

rem

aini

ng h

emat

olog

y pa

ram

eter

s; (b

) dup

licat

e ta

ble

for (

i) se

rum

che

mis

try,

(ii)

coag

ulat

ion

test

s (PT

, aPT

T an

d IN

R)

Onc

oMed

Pha

rmac

eutic

als,

Inc.

Stat

istic

al A

naly

sis P

lan

59R

5-00

3 (P

hase

2)

23

MA

R20

17

Conf

iden

tial

Pa

ge 7

8/14

9

Onc

oMed

Pha

rmac

eutic

als,

Inc.

Page

1 o

f x

59R

5-00

3 (P

hase

2)

Tab

le 1

4.3.

4.3

H

emat

olog

y –

Ran

ge C

hang

e A

bnor

mal

– H

igh

Sa

fety

Pop

ulat

ion

Labo

rato

ry P

aram

eter

Pl

aceb

o (N

=xx)

Ta

rext

umab

(N

=xx)

Hem

oglo

bin

(g/d

L)

n

xx (x

x.x%

) xx

(xx.

x%)

A

ny P

ost-B

asel

ine

[1]

Gra

de 4

xx

(xx.

x%)

xx (x

x.x%

)

G

rade

3

xx (x

x.x%

) xx

(xx.

x%)

Gra

de 2

xx

(xx.

x%)

xx (x

x.x%

)

G

rade

1

xx (x

x.x%

) xx

(xx.

x%)

Last

Obs

erva

tion

Post

-Bas

elin

e

G

rade

4

xx (x

x.x%

) xx

(xx.

x%)

Gra

de 3

xx

(xx.

x%)

xx (x

x.x%

)

G

rade

2

xx (x

x.x%

) xx

(xx.

x%)

Gra

de 1

xx

(xx.

x%)

xx (x

x.x%

)

Plat

elet

s (x1

0^9/

L)

[etc

eter

a]

[⁞]

[⁞]

[1

] Sub

ject

s are

cou

nted

onl

y on

ce u

sing

thei

r hig

hest

pos

t-bas

elin

e C

TCA

E se

verit

y gr

ade.

Onl

y pa

tient

s who

hav

e an

incr

ease

in C

TCA

E gr

ade

seve

rity

from

bas

elin

e ar

e co

nsid

ered

for c

ount

s of

Gra

des 1

thro

ugh

4. S

ubje

cts w

ho h

ave

a ba

selin

e re

sult

and

at le

ast o

ne p

ost-b

asel

ine

resu

lt fo

r a p

artic

ular

ana

lyte

are

con

side

red

whe

n de

term

inin

g pe

rcen

tage

s, re

gard

less

of w

heth

er th

e pa

tient

ha

d a

CTC

AE

grad

e co

unte

d fo

r the

ana

lyte

.

Prog

ram

mer

not

es: (

a) c

ontin

ue fo

r all

rem

aini

ng h

emat

olog

y pa

ram

eter

s with

CTC

AE s

ever

ity g

radi

ng c

rite

ria;

(b) d

uplic

ate

tabl

e fo

r (i)

seru

m c

hem

istr

y, (i

i) co

agul

atio

n te

sts (

PT, a

PTT

and

INR)

Onc

oMed

Pha

rmac

eutic

als,

Inc.

Stat

istic

al A

naly

sis P

lan

59R

5-00

3 (P

hase

2)

23

MA

R20

17

Conf

iden

tial

Pa

ge 7

9/14

9

Onc

oMed

Pha

rmac

eutic

als,

Inc.

Page

1 o

f x

59R

5-00

3 (P

hase

2)

Tab

le 1

4.3.

4.13

Uri

naly

sis –

Shi

ft fr

om B

asel

ine

Sa

fety

Pop

ulat

ion

Labo

rato

ry P

aram

eter

Tim

e Po

int

Pla

cebo

(N

= )

Ta

rext

umab

(N

= )

Pr

otei

n n

A

ny P

ost-B

asel

ine

Abs

ent t

o Pr

esen

t n

(%)

n (%

)

Last

Obs

erva

tion

Post

-Bas

elin

e

A

bsen

t to

Pres

ent

n (%

) n

(%)

Glu

cose

n

A

ny P

ost-B

asel

ine

Abs

ent t

o Pr

esen

t n

(%)

n (%

)

Last

Obs

erva

tion

Post

-Bas

elin

e

A

bsen

t to

Pres

ent

n (%

) n

(%)

pH

n

Any

Pos

t-Bas

elin

e

L

ow o

r Nor

mal

to H

igh

n (%

) n

(%)

Nor

mal

or H

igh

to L

ow

n (%

) n

(%)

La

st O

bser

vatio

n Po

st-B

asel

ine

Low

or N

orm

al to

Hig

h n

(%)

n (%

)

N

orm

al o

r Hig

h to

Low

n

(%)

n (%

)

Sp

ecifi

c G

ravi

ty

…

[1] B

asel

ine

is d

efin

ed a

s the

last

non

-mis

sing

val

ue p

rior t

o fir

st d

ose

of st

udy

drug

.

Onc

oMed

Pha

rmac

eutic

als,

Inc.

Stat

istic

al A

naly

sis P

lan

59R

5-00

3 (P

hase

2)

23

MA

R20

17

Conf

iden

tial

Pa

ge 8

0/14

9

Onc

oMed

Pha

rmac

eutic

als,

Inc.

Page

1 o

f x

59R

5-00

3 (P

hase

2)

Tab

le 1

4.3.

4.14

Vita

l Sig

ns

Sa

fety

Pop

ulat

ion

Pl

aceb

o (N

=xx)

Tare

xtum

ab (N

=xx)

Para

met

er

Tim

e Po

int

Res

ult

Cha

nge

from

B

asel

ine

R

esul

t C

hang

e fro

m

Bas

elin

e

Syst

olic

Blo

od P

ress

ure

(mm

Hg)

B

asel

ine

[1]

n

xx

xx

M

ean

(SD

) xx

.x (x

x.xx

)

xx

.x (x

x.xx

)

Med

ian

xx

xx

25

th, 7

5th P

erce

ntile

xx

, xx

xx, x

x

Min

, Max

xx

, xx

xx, x

x

Max

imum

Pos

t-Bas

elin

e

n xx

xx

xx

xx

Mea

n (S

D)

xx.x

(xx.

xx)

xx.x

(xx.

xx)

xx

.x (x

x.xx

) xx

.x (x

x.xx

)

M

edia

n xx

xx

xx

xx

25th

, 75th

Per

cent

ile

xx, x

x xx

, xx

xx

, xx

xx, x

x

M

in, M

ax

xx, x

x xx

, xx

xx

, xx

xx, x

x

M

inim

um P

ost-B

asel

ine

n

xx

xx

xx

xx

M

ean

(SD

) xx

.x (x

x.xx

) xx

.x (x

x.xx

)

xx.x

(xx.

xx)

xx.x

(xx.

xx)

Med

ian

xx

xx

xx

xx

25

th, 7

5th P

erce

ntile

xx

, xx

xx, x

x

xx, x

x xx

, xx

Min

, Max

xx

, xx

xx, x

x

xx, x

x xx

, xx

Last

Obs

erva

tion

Post

-Bas

elin

e

n xx

xx

xx

xx

Mea

n (S

D)

xx.x

(xx.

xx)

xx.x

(xx.

xx)

xx

.x (x

x.xx

) xx

.x (x

x.xx

)

M

edia

n xx

xx

xx

xx

25th

, 75th

Per

cent

ile

xx, x

x xx

, xx

xx

, xx

xx, x

x

M

in, M

ax

xx, x

x xx

, xx

xx

, xx

xx, x

x

Dia

stol

ic B

lood

Pre

ssur

e (m

mH

g)

Bas

elin

e [1

]

[etc

eter

a]

[⁞]

[⁞]

[⁞]

[⁞]

[⁞]

[1

] B

asel

ine

is d

efin

ed a

s the

last

non

-mis

sing

val

ue p

rior t

o fir

st d

ose

of st

udy

drug

.

Prog

ram

mer

not

es: (

a) c

ontin

ue fo

r all

vita

l sig

n pa

ram

eter

s (sy

stol

ic a

nd d

iasto

lic b

lood

pre

ssur

es, p

ulse

, bod

y te

mpe

ratu

re a

nd re

spir

atio

n ra

te)

Onc

oMed

Pha

rmac

eutic

als,

Inc.

Stat

istic

al A

naly

sis P

lan

59R

5-00

3 (P

hase

2)

23

MA

R20

17

Conf

iden

tial

Pa

ge 8

1/14

9

Onc

oMed

Pha

rmac

eutic

als,

Inc.

Page

1 o

f x

59R

5-00

3 (P

hase

2)

Tab

le 1

4.3.

4.15

Vita

l Sig

ns –

Ran

ge C

hang

e A

bnor

mal

(RC

A)

Sa

fety

Pop

ulat

ion

Vita

l Sig

ns P

aram

eter

Pl

aceb

o (N

=xx)

Ta

rext

umab

(N

=xx)

n xx

xx

A

ny P

ost-B

asel

ine

H

igh

[1]

Tem

pera

ture

xx

(xx.

x%)

xx (x

x.x%

)

Pu

lse

Rat

e xx

(xx.

x%)

xx (x

x.x%

)

R

espi

rato

ry R

ate

xx (x

x.x%

) xx

(xx.

x%)

SBP

xx (x

x.x%

) xx

(xx.

x%)

DB

P xx

(xx.

x%)

xx (x

x.x%

)

Lo

w [1

]

Te

mpe

ratu

re

xx (x

x.x%

) xx

(xx.

x%)

Puls

e R

ate

xx (x

x.x%

) xx

(xx.

x%)

Res

pira

tory

Rat

e

xx (x

x.x%

) xx

(xx.

x%)

SBP

xx (x

x.x%

) xx

(xx.

x%)

DB

P xx

(xx.

x%)

xx (x

x.x%

)

Last

Pos

t-Bas

elin

e V

isit

H

igh[1

]

Te

mpe

ratu

re

xx (x

x.x%

) xx

(xx.

x%)

Puls

e R

ate

xx

(xx.

x%)

xx (x

x.x%

)

R

espi

rato

ry R

ate

xx

(xx.

x%)

xx (x

x.x%

)

SB

P xx

(xx.

x%)

xx (x

x.x%

)

D

BP

xx (x

x.x%

) xx

(xx.

x%)

Low

[1]

Tem

pera

ture

xx

(xx.

x%)

xx (x

x.x%

)

Pu

lse

Rat

e

xx (x

x.x%

) xx

(xx.

x%)

Res

pira

tory

Rat

e

xx (x

x.x%

) xx

(xx.

x%)

SBP

xx (x

x.x%

) xx

(xx.

x%)

DB

P xx

(xx.

x%)

xx (x

x.x%

)

Not

e: S

BP=S

ysto

lic B

lood

Pre

ssur

e. D

BP=

Dia

stol

ic B

lood

Pre

ssur

e. N

orm

al R

ange

Tem

pera

ture

: 36.

6°C

to 3

7.3°

C. N

orm

al R

ange

SB

P: 9

0-12

0 m

mH

g. N

orm

al R

ange

DB

P: 6

0-80

mm

Hg.

Nor

mal

R

ange

Res

pira

tory

Rat

e: 1

2-18

bre

aths

per

min

ute.

Nor

mal

Ran

ge P

ulse

Rat

e: 6

0-10

0 be

ats p

er m

inut

e.

[1]

Each

subj

ect i

s rep

rese

nted

onc

e by

thei

r wor

st c

hang

e. A

rang

e ch

ange

can

be

eith

er a

cha

nge

in a

vita

l sig

n pa

ram

eter

val

ue fr

om b

asel

ine

low

or n

orm

al to

pos

t-bas

elin

e hi

gh o

r a c

hang

e fro

m

base

line

high

or n

orm

al to

pos

t-bas

elin

e lo

w. A

subj

ect c

an b

e in

clud

ed in

bot

h ‘H

igh’

and

‘Low

’ cat

egor

ies

if ap

plic

able

.

Onc

oMed

Pha

rmac

eutic

als,

Inc.

Stat

istic

al A

naly

sis P

lan

59R

5-00

3 (P

hase

2)

23

MA

R20

17

Conf

iden

tial

Pa

ge 8

2/14

9

Onc

oMed

Pha

rmac

eutic

als,

Inc.

Page

1 o

f x

59R

5-00

3 (P

hase

2)

Tab

le 1

4.3.

4.16

12-L

ead

Ele

ctro

card

iogr

am (E

CG

)

Safe

ty P

opul

atio

n

Plac

ebo

(N=x

x)

Ta

rext

umab

(N=x

x)

Para

met

er

Tim

e Po

int

Res

ult

Cha

nge

from

B

asel

ine

R

esul

t C

hang

e fro

m

Bas

elin

e

QR

S D

urat

ion

(mse

c)

Bas

elin

e [1

]

n xx

xx

Mea

n (S

D)

xx.x

(xx.

xx)

xx.x

(xx.

xx)

M

edia

n xx

xx

25th

, 75th

Per

cent

ile

xx, x

x

xx

, xx

M

in, M

ax

xx, x

x

xx

, xx

M

axim

um P

ost-B

asel

ine

n

xx

xx

xx

xx

M

ean

(SD

) xx

.x (x

x.xx

) xx

.x (x

x.xx

)

xx.x

(xx.

xx)

xx.x

(xx.

xx)

Med

ian

xx

xx

xx

xx

25

th, 7

5th P

erce

ntile

xx

, xx

xx, x

x

xx, x

x xx

, xx

Min

, Max

xx

, xx

xx, x

x

xx, x

x xx

, xx

Min

imum

Pos

t-Bas

elin

e

n xx

xx

xx

xx

Mea

n (S

D)

xx.x

(xx.

xx)

xx.x

(xx.

xx)

xx

.x (x

x.xx

) xx

.x (x

x.xx

)

M

edia

n xx

xx

xx

xx

25th

, 75th

Per

cent

ile

xx, x

x xx

, xx

xx

, xx

xx, x

x

M

in, M

ax

xx, x

x xx

, xx

xx

, xx

xx, x

x

La

st O

bser

vatio

n Po

st-B

asel

ine

n

xx

xx

xx

xx

M

ean

(SD

) xx

.x (x

x.xx

) xx

.x (x

x.xx

)

xx.x

(xx.

xx)

xx.x

(xx.

xx)

Med

ian

xx

xx

xx

xx

25

th, 7

5th P

erce

ntile

xx

, xx

xx, x

x

xx, x

x xx

, xx

Min

, Max

xx

, xx

xx, x

x

xx, x

x xx

, xx

PR

Inte

rval

(mse

c)

Bas

elin

e [1

]

[etc

eter

a]

[⁞]

[⁞]

[⁞]

[⁞]

[⁞]

[1

] B

asel

ine

is d

efin

ed a

s the

last

non

-mis

sing

val

ue p

rior t

o fir

st d

ose

of st

udy

drug

.

Prog

ram

mer

not

es: (

a) c

ontin

ue fo

r all

elec

troc

ardi

ogra

m p

aram

eter

s (Q

RS d

urat

ion,

PR

inte

rval

, QTc

Inte

rval

)

Onc

oMed

Pha

rmac

eutic

als,

Inc.

Stat

istic

al A

naly

sis P

lan

59R

5-00

3 (P

hase

2)

23

MA

R20

17

Conf

iden

tial

Pa

ge 8

3/14

9

Onc

oMed

Pha

rmac

eutic

als,

Inc.

Page

1 o

f x

59R

5-00

3 (P

hase

2)

Tab

le 1

4.3.

4.17

12-L

ead

Ele

ctro

card

iogr

am (E

CG

) – R

ange

Cha

nge

Abn

orm

al

Sa

fety

Pop

ulat

ion

ECG

Par

amet

er

Plac

ebo

(N=x

x)

Tare

xtum

ab

(N=x

x)

n

xx

xx

Any

Pos

t-Bas

elin

e

Hig

h [1

]

Q

RS

Dur

atio

n (m

sec)

xx

(xx.

x%)

xx (x

x.x%

)

PR

Inte

rval

(mse

c)

xx (x

x.x%

) xx

(xx.

x%)

QTc

Inte

rval

(mse

c)

xx (x

x.x%

) xx

(xx.

x%)

Low

[1]

QR

S D

urat

ion

(mse

c)

xx (x

x.x%

) xx

(xx.

x%)

PR In

terv

al (m

sec)

xx

(xx.

x%)

xx (x

x.x%

)

Q

Tc In

terv

al (m

sec)

xx

(xx.

x%)

xx (x

x.x%

)

Last

Obs

erva

tion

Post

-Bas

elin

e

Hig

h[1]

QR

S D

urat

ion

(mse

c)

xx (x

x.x%

) xx

(xx.

x%)

PR In

terv

al (m

sec)

xx

(xx.

x%)

xx (x

x.x%

)

Q

Tc In

terv

al (m

sec)

xx

(xx.

x%)

xx (x

x.x%

)

Lo

w[1

]

Q

RS

Dur

atio

n (m

sec)

xx

(xx.

x%)

xx (x

x.x%

)

PR

Inte

rval

(mse

c)

xx (x

x.x%

) xx

(xx.

x%)

QTc

Inte

rval

(mse

c)

xx (x

x.x%

) xx

(xx.

x%)

N

ote:

Ref

eren

ce ra

nges

: QR

S du

ratio

n 80

-100

mse

c; P

R in

terv

al 1

20-2

00 m

sec;

QTc

inte

rval

≤43

0 m

sec

(mal

es), ≤4

50 m

sec

(fem

ales

). [1

] Ea

ch su

bjec

t is r

epre

sent

ed o

nce

by th

eir w

orst

cha

nge.

A ra

nge

chan

ge c

an b

e ei

ther

a c

hang

e in

an

ECG

par

amet

er v

alue

from

bas

elin

e lo

w o

r nor

mal

to p

ost-b

asel

ine

high

or a

cha

nge

from

ba

selin

e hi

gh o

r nor

mal

to p

ost-b

asel

ine

low

. A su

bjec

t can

be

incl

uded

in b

oth

‘Hig

h’ a

nd ‘L

ow’ c

ateg

orie

s if f

its b

oth

cate

gorie

s.

Onc

oMed

Pha

rmac

eutic

als,

Inc.

Stat

istic

al A

naly

sis P

lan

59R

5-00

3 (P

hase

2)

23

MA

R20

17

Conf

iden

tial

Pa

ge 8

4/14

9

Onc

oMed

Pha

rmac

eutic

als,

Inc.

Page

1 o

f x

59R

5-00

3 (P

hase

2)

Tab

le 1

4.3.

4.18

12-L

ead

Ele

ctro

card

iogr

am (E

CG

) – Q

Tc

Inte

rval

Safe

ty P

opul

atio

n

Tim

e Po

int

Plac

ebo

(N=x

x)

Tare

xtum

ab

(N=x

x)

B

asel

ine

[1]

<4

80

xx (x

x.x%

) xx

(xx.

x%)

48

0-50

0 m

sec

xx (x

x.x%

) xx

(xx.

x%)

>5

00 m

sec

xx (x

x.x%

) xx

(xx.

x%)

W

orst

(Max

imum

) Po

st-B

asel

ine

<4

80

xx (x

x.x%

) xx

(xx.

x%)

48

0-50

0 m

sec

xx (x

x.x%

) xx

(xx.

x%)

>5

00 m

sec

xx (x

x.x%

) xx

(xx.

x%)

La

st O

bser

vatio

n Po

st-B

asel

ine

<4

80

xx (x

x.x%

) xx

(xx.

x%)

48

0-50

0 m

sec

xx (x

x.x%

) xx

(xx.

x%)

>5

00 m

sec

xx (x

x.x%

) xx

(xx.

x%)

[1

] Bas

elin

e is

def

ined

as t

he la

st n

on-m

issi

ng v

alue

prio

r to

first

dos

e of

stud

y dr

ug.

Onc

oMed

Pha

rmac

eutic

als,

Inc.

Stat

istic

al A

naly

sis P

lan

59R

5-00

3 (P

hase

2)

23

MA

R20

17

Conf

iden

tial

Pa

ge 8

5/14

9

Onc

oMed

Pha

rmac

eutic

als,

Inc.

Page

1 o

f x

59R

5-00

3 (P

hase

2)

Tab

le 1

4.3.

4.19

12-L

ead

Ele

ctro

card

iogr

am (E

CG

) – O

vera

ll In

terp

reta

tion

Sa

fety

Pop

ulat

ion

Tim

e Po

int

Plac

ebo

(N=

)

Tare

xtum

ab

(N=

)

B

asel

ine

[1]

n

n

n

Nor

mal

n

(%)

n (%

)

Abn

orm

al N

CS

n (%

) n

(%)

A

bnor

mal

CS

n (%

) n

(%)

W

orst

Pos

t-Bas

elin

e

n

n n

Nor

mal

n

(%)

n (%

) A

bnor

mal

NC

S n

(%)

n (%

)

Abn

orm

al C

S n

(%)

n (%

)

La

st O

bser

vatio

n Po

st-B

asel

ine

n

n n

Nor

mal

n

(%)

n (%

) A

bnor

mal

NC

S n

(%)

n (%

)

Abn

orm

al C

S n

(%)

n (%

)

N

ote:

NC

S =

Not

clin

ical

ly si

gnifi

cant

, CS

= C

linic

ally

sign

ifica

nt. P

erce

ntag

es a

re b

ased

on

the

num

ber o

f sub

ject

s with

a n

on-m

issi

ng re

spon

se a

t eac

h vi

sit.

[1] B

asel

ine

is d

efin

ed a

s the

last

non

-mis

sing

val

ue p

rior t

o fir

st d

ose

of st

udy

drug

.

Onc

oMed

Pha

rmac

eutic

als,

Inc.

Stat

istic

al A

naly

sis P

lan

59R

5-00

3 (P

hase

2)

23

MA

R20

17

Conf

iden

tial

Pa

ge 8

6/14

9

Onc

oMed

Pha

rmac

eutic

als,

Inc.

Page

1 o

f x

59R

5-00

3 (P

hase

2)

Tab

le 1

4.3.

4.20

12-L

ead

Ele

ctro

card

iogr

am (E

CG

) – O

vera

ll In

terp

reta

tion

Shift

from

Bas

elin

e

Safe

ty P

opul

atio

n

Bas

elin

e [1

] M

ost E

xtre

me

Post

-Bas

elin

e Pl

aceb

o (N

=xx)

Ta

rext

umab

(N

=xx)

N

orm

al

Nor

mal

xx

(xx.

x%)

xx (x

x.x%

)

Abn

orm

al -

Not

Clin

ical

ly S

igni

fican

t xx

(xx.

x%)

xx (x

x.x%

)

Abn

orm

al -

Clin

ical

ly S

igni

fican

t xx

(xx.

x%)

xx (x

x.x%

)

A

bnor

mal

- N

ot C

linic

ally

Sig

nific

ant

Nor

mal

xx

(xx.

x%)

xx (x

x.x%

)

Abn

orm

al -

Not

Clin

ical

ly S

igni

fican

t xx

(xx.

x%)

xx (x

x.x%

)

Abn

orm

al -

Clin

ical

ly S

igni

fican

t xx

(xx.

x%)

xx (x

x.x%

)

A

bnor

mal

- C

linic

ally

Sig

nific

ant

Nor

mal

xx

(xx.

x%)

xx (x

x.x%

)

Abn

orm

al -

Not

Clin

ical

ly S

igni

fican

t xx

(xx.

x%)

xx (x

x.x%

)

Abn

orm

al -

Clin

ical

ly S

igni

fican

t xx

(xx.

x%)

xx (x

x.x%

)

[1

] B

asel

ine

is d

efin

ed a

s the

last

non

-mis

sing

val

ue p

rior t

o fir

st d

ose

of st

udy

drug

.

Onc

oMed

Pha

rmac

eutic

als,

Inc.

Stat

istic

al A

naly

sis P

lan

59R

5-00

3 (P

hase

2)

23

MA

R20

17

Conf

iden

tial

Pa

ge 8

7/14

9

Onc

oMed

Pha

rmac

eutic

als,

Inc.

Page

1 o

f x

59R

5-00

3 (P

hase

2)

Tab

le 1

4.3.

4.21

EC

OG

Per

form

ance

Sta

tus

Sa

fety

Pop

ulat

ion

Perfo

rman

ce S

tatu

s Sco

re [1

] Pl

aceb

o (N

=xx)

Ta

rext

umab

(N

=xx)

Bas

elin

e [2

]

n xx

xx

0 xx

(xx.

x%)

xx (x

x.x%

)

1 xx

(xx.

x%)

xx (x

x.x%

)

2 xx

(xx.

x%)

xx (x

x.x%

)

3 xx

(xx.

x%)

xx (x

x.x%

)

4 xx

(xx.

x%)

xx (x

x.x%

)

5 xx

(xx.

x%)

xx (x

x.x%

)

Max

imum

Pos

t-Bas

elin

e

n xx

xx

0 xx

(xx.

x%)

xx (x

x.x%

)

1 xx

(xx.

x%)

xx (x

x.x%

)

2 xx

(xx.

x%)

xx (x

x.x%

)

3 xx

(xx.

x%)

xx (x

x.x%

)

4 xx

(xx.

x%)

xx (x

x.x%

)

5 xx

(xx.

x%)

xx (x

x.x%

)

Min

imum

Pos

t-Bas

elin

e

n xx

xx

0 xx

(xx.

x%)

xx (x

x.x%

)

1 xx

(xx.

x%)

xx (x

x.x%

)

2 xx

(xx.

x%)

xx (x

x.x%

)

3 xx

(xx.

x%)

xx (x

x.x%

)

4 xx

(xx.

x%)

xx (x

x.x%

)

5 xx

(xx.

x%)

xx (x

x.x%

)

Last

Obs

erva

tion

Post

-Bas

elin

e

n xx

xx

0 xx

(xx.

x%)

xx (x

x.x%

)

1 xx

(xx.

x%)

xx (x

x.x%

)

2 xx

(xx.

x%)

xx (x

x.x%

)

3 xx

(xx.

x%)

xx (x

x.x%

)

4 xx

(xx.

x%)

xx (x

x.x%

)

5 xx

(xx.

x%)

xx (x

x.x%

) N

ote:

Per

cent

ages

are

bas

ed o

n th

e nu

mbe

r of p

atie

nts w

ith a

non

-mis

sing

resp

onse

at e

ach

visi

t.

[1] F

or c

ompl

ete

defin

ition

s of e

ach

activ

ity st

atus

cod

e, re

fere

nce

App

endi

x D

of t

he c

linic

al p

roto

col.

[2] B

asel

ine

is d

efin

ed a

s the

last

non

-mis

sing

val

ue p

rior t

o fir

st d

ose

of st

udy

drug

.

Onc

oMed

Pha

rmac

eutic

als,

Inc.

Stat

istic

al A

naly

sis P

lan

59R

5-00

3 (P

hase

2)

23

MA

R20

17

Conf

iden

tial

Pa

ge 8

8/14

9

Onc

oMed

Pha

rmac

eutic

als,

Inc.

Page

1 o

f x

59R

5-00

3 (P

hase

2)

Tab

le 1

4.3.

4.22

E

CO

G P

erfo

rman

ce S

tatu

s – S

hift

from

Bas

elin

e Sa

fety

Pop

ulat

ion

Pe

rform

ance

Sta

tus S

core

[1]

Plac

ebo

(N=

)

Bas

elin

e [2

]

Tare

xtum

ab (N

= )

B

asel

ine

[2]

0 1

0

1

M

axim

um P

ost-B

asel

ine

n

n

n

n n

0

n

(%)

n (%

)

n (%

) n

(%)

1

n

(%)

n (%

)

n (%

) n

(%)

2

n

(%)

n (%

)

n (%

) n

(%)

3

n

(%)

n (%

)

n (%

) n

(%)

4

n

(%)

n (%

)

n (%

) n

(%)

5

n

(%)

n (%

)

n (%

) n

(%)

Min

imum

Pos

t-Bas

elin

e

n

n

n

n n

0

n

(%)

n (%

)

n (%

) n

(%)

1

n

(%)

n (%

)

n (%

) n

(%)

2

n

(%)

n (%

)

n (%

) n

(%)

3

n

(%)

n (%

)

n (%

) n

(%)

4

n

(%)

n (%

)

n (%

) n

(%)

5

n

(%)

n (%

)

n (%

) n

(%)

[1] F

or c

ompl

ete

defin

ition

s of e

ach

activ

ity st

atus

cod

e, re

fere

nce

App

endi

x D

of t

he c

linic

al p

roto

col.

[2]

Bas

elin

e is

def

ined

as t

he la

st n

on-m

issi

ng v

alue

prio

r to

first

dos

e of

stud

y dr

ug.

Prog

ram

min

g no

te: C

ontin

ue fo

r Las

t Obs

erva

tion

Post

-Bas

elin

e.

Prog

ram

min

g no

te: A

dd a

dditi

onal

bas

elin

e co

lum

ns a

s nee

ded.

Onc

oMed

Pha

rmac

eutic

als,

Inc.

Stat

istic

al A

naly

sis P

lan

59R

5-00

3 (P

hase

2)

23

MA

R20

17

Conf

iden

tial

Pa

ge 8

9/14

9

Onc

oMed

Pha

rmac

eutic

als,

Inc.

Page

1 o

f x

59R

5-00

3 (P

hase

2)

Tab

le 1

4.3.

4.23

Ant

i-Tar

extu

mab

Ant

ibod

ies

Im

mun

ogen

icity

Pop

ulat

ion

Tim

e Po

int

Tare

xtum

ab

(N=x

x)

Any

Pos

itive

Sam

ple

Dur

ing

Stud

y xx

(xx.

x%)

Cyc

le 1

, Day

1

Posi

tive

xx (x

x.x%

)

Neg

ativ

e xx

(xx.

x%)

V

iabl

e Sa

mpl

e N

ot A

vaila

ble

xx (x

x.x%

)

C

ycle

3, D

ay 1

Po

sitiv

e xx

(xx.

x%)

N

egat

ive

xx (x

x.x%

)

Via

ble

Sam

ple

Not

Ava

ilabl

e xx

(xx.

x%)

Cyc

le 5

, Day

1

Posi

tive

xx (x

x.x%

)

Neg

ativ

e xx

(xx.

x%)

V

iabl

e Sa

mpl

e N

ot A

vaila

ble

xx (x

x.x%

)

Tr

eatm

ent T

erm

inat

ion

Posi

tive

xx (x

x.x%

)

Neg

ativ

e xx

(xx.

x%)

V

iabl

e Sa

mpl

e N

ot A

vaila

ble

xx (x

x.x%

)

Onc

oMed

Pha

rmac

eutic

als,

Inc.

Stat

istic

al A

naly

sis P

lan

59R

5-00

3 (P

hase

2)

23

MA

R20

17

Conf

iden

tial

Pa

ge 9

0/14

9

Onc

oMed

Pha

rmac

eutic

als,

Inc.

Page

1 o

f x

59R

5-00

3 (P

hase

2)

Tab

le 1

4.3.

4.24

Impa

ct o

f Ant

i-Tar

extu

mab

Ant

ibod

ies o

n Pr

ogre

ssio

n-Fr

ee S

urvi

val

Im

mun

ogen

icity

Pop

ulat

ion

Tare

xtum

ab (N

=xx)

Ant

i-Tar

extu

mab

A

ntib

ody

Neg

ativ

e (N

=xx)

Ant

i-Tar

extu

mab

A

ntib

ody

Posi

tive

(N=x

x)

To

tal F

ollo

w-U

p Ti

me

(per

son-

year

s) [1

] xx

x.x

xxx.

x N

umbe

r of S

ubje

cts w

ith D

isea

se P

rogr

essi

on o

r Dea

th

xx (x

x.x%

) xx

(xx.

x%)

Num

ber o

f Sub

ject

s who

did

not

Pro

gres

s or D

ie (C

enso

red)

xx

(xx.

x%)

xx (x

x.x%

)

Haz

ard

[2]

0.xx

0.

xx

K

apla

n-M

eier

Est

imat

es: Q

uarti

les [

95%

C.I.

] (da

ys)

25

th P

erce

ntile

xx

x [x

xx,x

xx]

xxx

[xxx

,xxx

]

50th

Per

cent

ile

xxx

[xxx

,xxx

] xx

x [x

xx,x

xx]

75

th P

erce

ntile

xx

x [x

xx,x

xx]

xxx

[xxx

,xxx

]

Ran

ge (S

ubje

cts w

ho P

rogr

esse

d or

Die

d) (d

ays)

xx

x, x

xx

xxx,

xxx

R

ange

(All

Subj

ects

) (da

ys)

xxx,

xxx

xx

x, x

xx

H

azar

d R

atio

[95%

C.I.

] [3]

x.

xx [x

.xx,

x.xx

] P-

valu

e [4

]

0.xx

x

Not

e: P

FS=

Dat

e of

Doc

umen

tatio

n of

Dea

th/P

rogr

essi

on –

Ran

dom

izat

ion

Dat

e +

1. S

ubje

cts w

ho h

ad n

ot e

xper

ienc

ed d

eath

or p

rogr

essi

on b

y th

eir l

ast c

onta

ct w

ere

cens

ored

at t

he ti

me

of th

eir l

ast

radi

ogra

phic

resp

onse

ass

essm

ent.

Subj

ects

lack

ing

a ra

diog

raph

ic re

spon

se a

sses

smen

t afte

r ran

dom

izat

ion

who

do

not p

rogr

ess o

r die

hav

e th

eir e

vent

tim

e ce

nsor

ed o

n th

e da

te o

f ran

dom

izat

ion

with

dur

atio

n of

1 d

ay. F

or d

etai

led

even

t and

cen

sorin

g ru

les r

efer

to p

roto

col s

ectio

n 13

.5.1

and

SA

P se

ctio

n 8.

1. C

.I. =

Con

fiden

ce In

terv

al.

[1] Su

m o

f all

indi

vidu

al fo

llow

-up

times

in d

ays d

ivid

ed b

y 36

5.25

. [2

] N

umbe

r of S

ubje

cts w

ith D

isea

se P

rogr

essi

on o

r Dea

th/ T

otal

Fol

low

-up

Tim

e (P

erso

n-ye

ars)

. [3

] H

azar

d ra

tio a

nd 9

5% C

.I. fr

om C

ox p

ropo

rtion

al h

azar

ds m

odel

with

mai

n ef

fect

s for

ant

i-tar

extu

mab

ant

ibod

y st

atus

(pos

itive

or n

egat

ive)

. [4

] P-

valu

e fo

r tre

atm

ent e

ffec

t fro

m u

nstra

tifie

d lo

g ra

nk te

st.

Prog

ram

mer

not

es: (

a) p

erce

ntag

es a

re b

ased

on

the

num

bers

of s

ubje

cts w

ho a

re a

ntib

ody

nega

tive

and

antib

ody

posit

ive,

not

on

the

num

ber o

f sub

ject

s rec

eivi

ng ta

rext

umab

Onc

oMed

Pha

rmac

eutic

als,

Inc.

Stat

istic

al A

naly

sis P

lan

59R

5-00

3 (P

hase

2)

23

MA

R20

17

Conf

iden

tial

Pa

ge 9

1/14

9

Onc

oMed

Pha

rmac

eutic

als,

Inc.

Page

1 o

f x

59R

5-00

3 (P

hase

2)

Tab

le 1

4.3.

4.25

Impa

ct o

f Ant

i-Tar

extu

mab

Ant

ibod

ies o

n O

vera

ll Su

rviv

al

Im

mun

ogen

icity

Pop

ulat

ion

Tare

xtum

ab (N

=xx)

Ant

i-Tar

extu

mab

A

ntib

ody

Neg

ativ

e (N

=xx)

Ant

i-Tar

extu

mab

A

ntib

ody

Posi

tive

(N=x

x)

To

tal F

ollo

w-U

p Ti

me

(per

son-

year

s) [1

] xx

x.x

xxx.

x N

umbe

r of S

ubje

cts w

ho D

ied

xx (x

x.x%

) xx

(xx.

x%)

Num

ber o

f Sub

ject

s who

did

not

Die

(Cen

sore

d)

xx (x

x.x%

) xx

(xx.

x%)

H

azar

d [2

] 0.

xx

0.xx

Kap

lan-

Mei

er E

stim

ates

: [95

% C

.I.] (

days

)

25th

Per

cent

ile

xxx

[xxx

,xxx

] xx

x [x

xx,x

xx]

50

th P

erce

ntile

(Med

ian)

xx

x [x

xx,x

xx]

xxx

[xxx

,xxx

]

75th

Per

cent

ile

xxx

[xxx

,xxx

] xx

x [x

xx,x

xx]

K

apla

n-M

eier

Est

imat

e (#

at r

isk)

[SE]

180

Day

s 0.

xx (x

x) [x

.xx]

0.

xx (x

x) [x

.xx]

360

Day

s 0.

xx (x

x) [x

.xx]

0.

xx (x

x) [x

.xx]

540

Day

s 0.

xx (x

x) [x

.xx]

0.

xx (x

x) [x

.xx]

720

Day

s 0.

xx (x

x) [x

.xx]

0.

xx (x

x) [x

.xx]

Ran

ge (S

ubje

cts w

ho D

ied)

(day

s)

xxx,

xxx

xx

x, x

xx

Ran

ge (A

ll Su

bjec

ts) (

days

) xx

x, x

xx

xxx,

xxx

Haz

ard

Rat

io [9

5% C

.I.] [3

]

x.xx

[x.x

x,x.

xx]

P-va

lue

[4]

0.

xxx

N

ote:

Ove

rall

Surv

ival

= D

ate

of D

ocum

enta

tion

of D

eath

– R

ando

miz

atio

n D

ate

+ 1.

Sub

ject

s who

had

not

exp

erie

nced

dea

th b

y th

eir l

ast c

onta

ct d

ate

wer

e ce

nsor

ed a

t tha

t tim

e. S

ubje

cts l

acki

ng

data

afte

r ran

dom

izat

ion

who

do

not d

ie h

ave

thei

r eve

nt ti

me

cens

ored

on

the

date

of r

ando

miz

atio

n w

ith d

urat

ion

of 1

day

. For

det

aile

d ev

ent a

nd c

enso

ring

rule

s ref

er to

pro

toco

l sec

tion

13.5

.4 a

nd

SAP

sect

ion

8.6.

C.I.

= C

onfid

ence

Inte

rval

. SE

= St

anda

rd E

rror.

[1] Su

m o

f all

indi

vidu

al fo

llow

-up

times

in d

ays d

ivid

ed b

y 36

5.25

. [2

] Num

ber o

f Sub

ject

s who

Die

d/ T

otal

Fol

low

-up

Tim

e (P

erso

n-ye

ars)

. [3

] H

azar

d ra

tio a

nd 9

5% C

.I. fr

om C

ox p

ropo

rtion

al h

azar

ds m

odel

with

mai

n ef

fect

s for

ant

i-tar

extu

mab

ant

ibod

y st

atus

(pos

itive

or n

egat

ive)

. [4

] P-

valu

e fo

r tre

atm

ent e

ffec

t fro

m u

nstra

tifie

d lo

g ra

nk te

st.

Prog

ram

mer

not

es: (

a) p

erce

ntag

es a

re b

ased

on

the

num

bers

of s

ubje

cts w

ho a

re a

ntib

ody

nega

tive

and

antib

ody

posit

ive,

not

on

the

num

ber o

f sub

ject

s rec

eivi

ng ta

rext

umab

Onc

oMed

Pha

rmac

eutic

als,

Inc.

Stat

istic

al A

naly

sis P

lan

59R

5-00

3 (P

hase

2)

23

MA

R20

17

Conf

iden

tial

Pa

ge 9

2/14

9

Onc

oMed

Pha

rmac

eutic

als,

Inc.

Page

1 o

f x

59R

5-00

3 (P

hase

2)

Tab

le 1

4.3.

4.26

Ove

rall

Sum

mar

y of

Im

pact

of A

nti-T

arex

tum

ab A

ntib

odie

s on

Tre

atm

ent-

Em

erge

nt A

dver

se E

vent

s (T

EA

Es)

Imm

unog

enic

ity P

opul

atio

n

Ta

rext

umab

(N=x

x)

Ant

i-Tar

extu

mab

A

ntib

ody

Neg

ativ

e (N

=xx)

Ant

i-Tar

extu

mab

A

ntib

ody

Posi

tive

(N=x

x)

Su

bjec

ts R

epor

ting

at L

east

One

TEA

E xx

(xx.

x%)

xx (x

x.x%

)

Subj

ects

Rep

ortin

g at

Lea

st O

ne S

erio

us T

EAE

xx (x

x.x%

) xx

(xx.

x%)

Subj

ects

Rep

ortin

g at

Lea

st O

ne S

erio

us T

EAE

Rel

ated

to T

arex

tum

ab

xx (x

x.x%

) xx

(xx.

x%)

Subj

ects

Rep

ortin

g at

Lea

st O

ne S

erio

us T

EAE

Rel

ated

to E

topo

side

xx (x

x.x%

) xx

(xx.

x%)

Subj

ects

Rep

ortin

g at

Lea

st O

ne S

erio

us T

EAE

Rel

ated

to P

latin

um T

hera

py

xx (x

x.x%

) xx

(xx.

x%)

Su

bjec

ts R

epor

ting

at L

east

One

Gra

de 3

or H

ighe

r TEA

E xx

(xx.

x%)

xx (x

x.x%

) Su

bjec

ts R

epor

ting

at L

east

One

Gra

de 4

or H

ighe

r TEA

E xx

(xx.

x%)

xx (x

x.x%

)

Subj

ects

Rep

ortin

g TE

AE

Lead

ing

to D

elay

/Inte

rrup

tion

of T

arex

tum

ab

xx (x

x.x%

) xx

(xx.

x%)

Subj

ects

Rep

ortin

g TE

AE

Lead

ing

to D

elay

/Inte

rrup

tion

of E

topo

side

xx (x

x.x%

) xx

(xx.

x%)

Subj

ects

Rep

ortin

g TE

AE

Lead

ing

to D

elay

/Inte

rrup

tion

of P

latin

um T

hera

py

xx (x

x.x%

) xx

(xx.

x%)

Su

bjec

ts R

epor

ting

TEA

E Le

adin

g to

Dos

e R

educ

tion

of T

arex

tum

ab

xx (x

x.x%

) xx

(xx.

x%)

Subj

ects

Rep

ortin

g TE

AE

Lead

ing

to D

ose

Red

uctio

n of

Eto

posid

e xx

(xx.

x%)

xx (x

x.x%

) Su

bjec

ts R

epor

ting

TEA

E Le

adin

g to

Dos

e R

educ

tion

of P

latin

um T

hera

py

xx (x

x.x%

) xx

(xx.

x%)

Su

bjec

ts R

epor

ting

TEA

E Le

adin

g to

With

draw

al o

f Tar

extu

mab

xx

(xx.

x%)

xx (x

x.x%

) Su

bjec

ts R

epor

ting

TEA

E Le

adin

g to

With

draw

al o

f Eto

posid

e xx

(xx.

x%)

xx (x

x.x%

) Su

bjec

ts R

epor

ting

TEA

E Le

adin

g to

With

draw

al o

f Pla

tinum

The

rapy

xx

(xx.

x%)

xx (x

x.x%

)

Subj

ects

Rep

ortin

g TE

AE

with

Out

com

e of

Dea

th

xx (x

x.x%

) xx

(xx.

x%)

M

axim

um C

TCA

E Se

verit

y G

rade

[1]

G

rade

1

xx (x

x.x%

) xx

(xx.

x%)

G

rade

2

xx (x

x.x%

) xx

(xx.

x%)

G

rade

3

xx (x

x.x%

) xx

(xx.

x%)

G

rade

4

xx (x

x.x%

) xx

(xx.

x%)

G

rade

5

xx (x

x.x%

) xx

(xx.

x%)

[1

] CTC

AE

= C

omm

on T

erm

inol

ogy

Crit

eria

for A

dver

se E

vent

s (ve

rsio

n 4.

02).

Subj

ects

with

mor

e th

an o

ne T

EAE

are

coun

ted

only

onc

e at

the

high

est C

TCA

E se

verit

y gr

ade

acro

ss a

ll TE

AEs

.

Prog

ram

mer

not

es: (

a) p

erce

ntag

es a

re b

ased

on

the

num

bers

of s

ubje

cts w

ho a

re a

ntib

ody

nega

tive

and

antib

ody

posit

ive,

not

on

the

num

ber o

f sub

ject

s rec

eivi

ng ta

rext

umab

Onc

oMed

Pha

rmac

eutic

als,

Inc.

Stat

istic

al A

naly

sis P

lan

59R

5-00

3 (P

hase

2)

23

MA

R20

17

Conf

iden

tial

Pa

ge 9

3/14

9

Onc

oMed

Pha

rmac

eutic

als,

Inc.

Page

1 o

f x

59R

5-00

3 (P

hase

2)

Tab

le 1

4.3.

4.27

Impa

ct o

f Ant

i-Tar

extu

mab

Ant

ibod

ies T

reat

men

t-E

mer

gent

Adv

erse

Eve

nts (

TE

AE

s)

Sa

fety

Pop

ulat

ion

Tare

xtum

ab (N

=xx)

Pref

erre

d Te

rm

Ant

i-Tar

extu

mab

A

ntib

ody

Neg

ativ

e (N

=xx)

Ant

i-Tar

extu

mab

A

ntib

ody

Posi

tive

(N=x

x)

Su

bjec

ts R

epor

ting

at L

east

One

TEA

E xx

(xx.

x%)

xx (x

x.x%

)

Pref

erre

d Te

rm 1

xx

(xx.

x%)

xx (x

x.x%

) Pr

efer

red

Term

2

xx (x

x.x%

) xx

(xx.

x%)

Pref

erre

d Te

rm 3

xx

(xx.

x%)

xx (x

x.x%

) Pr

efer

red

Term

4

xx (x

x.x%

) xx

(xx.

x%)

Pref

erre

d Te

rm 5

xx

(xx.

x%)

xx (x

x.x%

) Pr

efer

red

Term

6

xx (x

x.x%

) xx

(xx.

x%)

[etc

eter

a]

[⁞]

[⁞]

N

ote:

At e

ach

leve

l of s

umm

atio

n (o

vera

ll an

d pr

efer

red

term

), su

bjec

ts re

porti

ng m

ore

than

one

qua

lifyi

ng e

vent

are

cou

nted

onl

y on

ce.

Prog

ram

mer

not

es: (

a) p

erce

ntag

es a

re b

ased

on

the

num

bers

of s

ubje

cts w

ho a

re a

ntib

ody

nega

tive

and

antib

ody

posit

ive,

not

on

the

num

ber o

f sub

ject

s rec

eivi

ng ta

rext

umab

Onc

oMed

Pha

rmac

eutic

als,

Inc.

Stat

istic

al A

naly

sis P

lan

59R

5-00

3 (P

hase

2)

23

MA

R20

17

Conf

iden

tial

Pa

ge 9

4/14

9

Onc

oMed

Pha

rmac

eutic

als,

Inc.

Page

1 o

f x

59R

5-00

3 (P

hase

2)

Tab

le 1

4.3.

5.1

St

udy

Dru

g Ex

posu

re –

Tar

extu

mab

/Pla

cebo

Safe

ty P

opul

atio

n

Pl

aceb

o (N

=xx)

Ta

rext

umab

(N

=xx)

Trea

tmen

t Cyc

les

n

xx

xx

M

ean

(SD

) xx

.x (x

x.xx

) xx

.x (x

x.xx

)

Med

ian

xx

xx

25

th, 7

5th P

erce

ntile

xx

, xx

xx, x

x

Min

, Max

xx

, xx

xx, x

x

Num

ber o

f Inf

usio

ns A

dmin

iste

red

n

xx

xx

M

ean

(SD

) xx

.x (x

x.xx

) xx

.x (x

x.xx

)

Med

ian

xx

xx

25

th, 7

5th P

erce

ntile

xx

, xx

xx, x

x

Min

, Max

xx

, xx

xx, x

x

Tota

l Dos

e A

dmin

iste

red

(mg)

[1]

n

xx

xx

M

ean

(SD

) xx

.x (x

x.xx

) xx

.x (x

x.xx

)

Med

ian

xx

xx

25

th, 7

5th P

erce

ntile

xx

, xx

xx, x

x

Min

, Max

xx

, xx

xx, x

x

Dur

atio

n of

Tre

atm

ent (

days

) [2]

n

xx

xx

M

ean

(SD

) xx

.x (x

x.xx

) xx

.x (x

x.xx

)

Med

ian

xx

xx

25

th, 7

5th P

erce

ntile

xx

, xx

xx, x

x

Min

, Max

xx

, xx

xx, x

x

Dos

e In

tens

ity

n

xx

xx

M

ean

(SD

) xx

.x (x

x.xx

) xx

.x (x

x.xx

)

Med

ian

xx

xx

25

th, 7

5th P

erce

ntile

xx

, xx

xx, x

x

Min

, Max

xx

, xx

xx, x

x

[1] Pl

aceb

o ex

posu

re is

sum

mar

ized

in ta

rext

umab

-equ

ival

ent u

nits

(i.e

., th

e nu

mbe

r of m

illig

ram

s of t

arex

tum

ab th

e pl

aceb

o “r

epla

ced”

dur

ing

treat

men

t-blin

ded

dosi

ng).

[2] D

urat

ion

of tr

eatm

ent =

num

ber o

f day

s fro

m th

e fir

st d

ose

(Day

1) u

ntil

the

last

dos

e.

Onc

oMed

Pha

rmac

eutic

als,

Inc.

Stat

istic

al A

naly

sis P

lan

59R

5-00

3 (P

hase

2)

23

MA

R20

17

Conf

iden

tial

Pa

ge 9

5/14

9

Onc

oMed

Pha

rmac

eutic

als,

Inc.

Page

1 o

f x

59R

5-00

3 (P

hase

2)

Tab

le 1

4.3.

5.2

D

osin

g C

ompl

ianc

e –

Tar

extu

mab

/Pla

cebo

Safe

ty P

opul

atio

n

Pl

aceb

o (N

=xx)

Ta

rext

umab

(N

=xx)

Dos

ing

Com

plia

nce

(%) [1

]

n xx

xx

Mea

n (S

D)

xx.x

(xx.

xx)

xx.x

(xx.

xx)

M

edia

n xx

xx

25th

, 75t

h Pe

rcen

tile

xx, x

x xx

, xx

M

in, M

ax

xx, x

x xx

, xx

0%

to <

20%

Dos

ing

Com

plia

nce

xx (x

x.x%

) xx

(xx.

x%)

20%

to <

40%

Dos

ing

Com

plia

nce

xx (x

x.x%

) xx

(xx.

x%)

40%

to <

60%

Dos

ing

Com

plia

nce

xx (x

x.x%

) xx

(xx.

x%)

60%

to <

80%

Dos

ing

Com

plia

nce

xx (x

x.x%

) xx

(xx.

x%)

80%

to <

100%

Dos

ing

Com

plia

nce

xx (x

x.x%

) xx

(xx.

x%)

100%

Dos

ing

Com

plia

nce

xx (x

x.x%

) xx

(xx.

x%)

N

umbe

r of M

isse

d D

oses

xx

xx

R

easo

n fo

r Mis

sed

Dos

e

Adv

erse

Eve

nt

xx

xx

O

ther

xx

xx

Num

ber o

f Del

ayed

Dos

es

xx

xx

Rea

son

for D

elay

ed D

ose

A

dver

se E

vent

xx

xx

Oth

er

xx

xx

N

umbe

r of R

educ

ed D

oses

xx

xx

R

easo

n fo

r Red

uced

Dos

e

Adv

erse

Eve

nt

xx

xx

O

ther

xx

xx

[1] D

osin

g co

mpl

ianc

e =

(num

ber o

f dos

es a

dmin

iste

red)

/ nu

mbe

r of p

lann

ed d

oses

x 1

00.

Onc

oMed

Pha

rmac

eutic

als,

Inc.

Stat

istic

al A

naly

sis P

lan

59R

5-00

3 (P

hase

2)

23

MA

R20

17

Conf

iden

tial

Pa

ge 9

6/14

9

Onc

oMed

Pha

rmac

eutic

als,

Inc.

Page

1 o

f x

59R

5-00

3 (P

hase

2)

Tab

le 1

4.3.

5.3

St

udy

Dru

g Ex

posu

re –

Eto

posi

de

Sa

fety

Pop

ulat

ion

Pl

aceb

o (N

=xx)

Ta

rext

umab

(N

=xx)

Trea

tmen

t Cyc

les

n

xx

xx

M

ean

(SD

) xx

.x (x

x.xx

) xx

.x (x

x.xx

)

Med

ian

xx

xx

25

th, 7

5th P

erce

ntile

xx

, xx

xx, x

x

Min

, Max

xx

, xx

xx, x

x

Num

ber o

f Inf

usio

ns A

dmin

iste

red

n

xx

xx

M

ean

(SD

) xx

.x (x

x.xx

) xx

.x (x

x.xx

)

Med

ian

xx

xx

25

th, 7

5th P

erce

ntile

xx

, xx

xx, x

x

Min

, Max

xx

, xx

xx, x

x

Tota

l Dos

e A

dmin

iste

red

(mg)

n xx

xx

Mea

n (S

D)

xx.x

(xx.

xx)

xx.x

(xx.

xx)

M

edia

n xx

xx

25th

, 75th

Per

cent

ile

xx, x

x xx

, xx

M

in, M

ax

xx, x

x xx

, xx

D

urat

ion

of T

reat

men

t (da

ys) [1

]

n xx

xx

Mea

n (S

D)

xx.x

(xx.

xx)

xx.x

(xx.

xx)

M

edia

n xx

xx

25th

, 75th

Per

cent

ile

xx, x

x xx

, xx

M

in, M

ax

xx, x

x xx

, xx

D

ose

Inte

nsity

n xx

xx

Mea

n (S

D)

xx.x

(xx.

xx)

xx.x

(xx.

xx)

M

edia

n xx

xx

25th

, 75th

Per

cent

ile

xx, x

x xx

, xx

M

in, M

ax

xx, x

x xx

, xx

[1

] D

urat

ion

of tr

eatm

ent =

num

ber o

f day

s fro

m th

e fir

st d

ose

(Day

1) u

ntil

the

last

dos

e.

Onc

oMed

Pha

rmac

eutic

als,

Inc.

Stat

istic

al A

naly

sis P

lan

59R

5-00

3 (P

hase

2)

23

MA

R20

17

Conf

iden

tial

Pa

ge 9

7/14

9

Onc

oMed

Pha

rmac

eutic

als,

Inc.

Page

1 o

f x

59R

5-00

3 (P

hase

2)

Tab

le 1

4.3.

5.4

D

osin

g C

ompl

ianc

e –

Eto

posi

de

Sa

fety

Pop

ulat

ion

Pl

aceb

o (N

=xx)

Ta

rext

umab

(N

=xx)

Dos

ing

Com

plia

nce

[1]

n

xx

xx

M

ean

(SD

) xx

.x (x

x.xx

) xx

.x (x

x.xx

)

Med

ian

xx

xx

25

th, 7

5th P

erce

ntile

xx

, xx

xx, x

x

Min

, Max

xx

, xx

xx, x

x

0% to

<20

% D

osin

g Co

mpl

ianc

e xx

(xx.

x%)

xx (x

x.x%

) 20

% to

<40

% D

osin

g C

ompl

ianc

e xx

(xx.

x%)

xx (x

x.x%

) 40

% to

<60

% D

osin

g C

ompl

ianc

e xx

(xx.

x%)

xx (x

x.x%

) 60

% to

<80

% D

osin

g C

ompl

ianc

e xx

(xx.

x%)

xx (x

x.x%

) 80

% to

<10

0% D

osin

g Co

mpl

ianc

e xx

(xx.

x%)

xx (x

x.x%

) 10

0% D

osin

g C

ompl

ianc

e xx

(xx.

x%)

xx (x

x.x%

)

Num

ber o

f Mis

sed

Dos

es

xx

xx

Rea

son

for M

isse

d D

ose

A

dver

se E

vent

xx

xx

Oth

er

xx

xx

N

umbe

r of D

elay

ed D

oses

xx

xx

R

easo

n fo

r Del

ayed

Dos

e

Adv

erse

Eve

nt

xx

xx

O

ther

xx

xx

[1] D

osin

g co

mpl

ianc

e =

(num

ber o

f dos

es a

dmin

iste

red)

/ nu

mbe

r of p

lann

ed d

oses

.

Onc

oMed

Pha

rmac

eutic

als,

Inc.

Stat

istic

al A

naly

sis P

lan

59R

5-00

3 (P

hase

2)

23

MA

R20

17

Conf

iden

tial

Pa

ge 9

8/14

9

Onc

oMed

Pha

rmac

eutic

als,

Inc.

Page

1 o

f x

59R

5-00

3 (P

hase

2)

Tab

le 1

4.3.

5.5

St

udy

Dru

g Ex

posu

re –

Cis

plat

in

Sa

fety

Pop

ulat

ion

Pl

aceb

o (N

=xx)

Ta

rext

umab

(N

=xx)

Plat

inum

The

rapy

[1]

C

ispl

atin

xx

(xx.

x%)

xx (x

x.x%

)

Car

bopl

atin

xx

(xx.

x%)

xx (x

x.x%

)

Trea

tmen

t Cyc

les

n

xx

xx

M

ean

(SD

) xx

.x (x

x.xx

) xx

.x (x

x.xx

)

Med

ian

xx

xx

25

th, 7

5th P

erce

ntile

xx

, xx

xx, x

x

Min

, Max

xx

, xx

xx, x

x

Num

ber o

f Inf

usio

ns A

dmin

iste

red

n

xx

xx

M

ean

(SD

) xx

.x (x

x.xx

) xx

.x (x

x.xx

)

Med

ian

xx

xx

25

th, 7

5th P

erce

ntile

xx

, xx

xx, x

x

Min

, Max

xx

, xx

xx, x

x

Tota

l Dos

e A

dmin

iste

red

(mg)

n xx

xx

Mea

n (S

D)

xx.x

(xx.

xx)

xx.x

(xx.

xx)

M

edia

n xx

xx

25th

, 75th

Per

cent

ile

xx, x

x xx

, xx

M

in, M

ax

xx, x

x xx

, xx

D

urat

ion

of T

reat

men

t (da

ys) [2

]

n xx

xx

Mea

n (S

D)

xx.x

(xx.

xx)

xx.x

(xx.

xx)

M

edia

n xx

xx

25th

, 75th

Per

cent

ile

xx, x

x xx

, xx

M

in, M

ax

xx, x

x xx

, xx

D

ose

Inte

nsity

n xx

xx

Mea

n (S

D)

xx.x

(xx.

xx)

xx.x

(xx.

xx)

M

edia

n xx

xx

25th

, 75th

Per

cent

ile

xx, x

x xx

, xx

M

in, M

ax

xx, x

x xx

, xx

Onc

oMed

Pha

rmac

eutic

als,

Inc.

Stat

istic

al A

naly

sis P

lan

59R

5-00

3 (P

hase

2)

23

MA

R20

17

Conf

iden

tial

Pa

ge 9

9/14

9

[1] A

naly

ses p

rese

nted

in th

is ta

ble

incl

ude

only

subj

ects

who

rece

ived

cis

plat

in a

s the

ir pl

atin

um th

erap

y. P

erce

ntag

es b

elow

the

first

set o

f row

s are

bas

ed o

n su

bjec

ts w

ho re

ceiv

ed c

ispl

atin

. [2

] D

urat

ion

of tr

eatm

ent =

num

ber o

f day

s fro

m th

e fir

st d

ose

(Day

1) u

ntil

the

last

dos

e.

Prog

ram

mer

not

es: (

a) p

rodu

ce th

e sa

me

tabl

e re

plac

ing

“cis

plat

in”

with

“ca

rbop

latin

” in

the

title

and

foot

note

Onc

oMed

Pha

rmac

eutic

als,

Inc.

Stat

istic

al A

naly

sis P

lan

59R

5-00

3 (P

hase

2)

23

MA

R20

17

Conf

iden

tial

Pa

ge 1

00/1

49

Onc

oMed

Pha

rmac

eutic

als,

Inc.

Page

1 o

f x

59R

5-00

3 (P

hase

2)

Tab

le 1

4.3.

5.6

D

osin

g C

ompl

ianc

e –

Cis

plat

in

Sa

fety

Pop

ulat

ion

Pl

aceb

o (N

=xx)

Ta

rext

umab

(N

=xx)

Dos

ing

Com

plia

nce

[1]

n

xx

xx

M

ean

(SD

) xx

.x (x

x.xx

) xx

.x (x

x.xx

)

Med

ian

xx

xx

25

th, 7

5th P

erce

ntile

xx

, xx

xx, x

x

Min

, Max

xx

, xx

xx, x

x

0% to

<20

% D

osin

g Co

mpl

ianc

e xx

(xx.

x%)

xx (x

x.x%

) 20

% to

<40

% D

osin

g C

ompl

ianc

e xx

(xx.

x%)

xx (x

x.x%

) 40

% to

<60

% D

osin

g C

ompl

ianc

e xx

(xx.

x%)

xx (x

x.x%

) 60

% to

<80

% D

osin

g C

ompl

ianc

e xx

(xx.

x%)

xx (x

x.x%

) 80

% to

<10

0% D

osin

g Co

mpl

ianc

e xx

(xx.

x%)

xx (x

x.x%

) 10

0% D

osin

g C

ompl

ianc

e xx

(xx.

x%)

xx (x

x.x%

)

Num

ber o

f Mis

sed

Dos

es

xx

xx

Rea

son

for M

isse

d D

ose

A

dver

se E

vent

xx

xx

Oth

er

xx

xx

N

umbe

r of D

elay

ed D

oses

xx

xx

R

easo

n fo

r Del

ayed

Dos

e

Adv

erse

Eve

nt

xx

xx

O

ther

xx

xx

[1] D

osin

g co

mpl

ianc

e =

(num

ber o

f dos

es a

dmin

iste

red)

/ nu

mbe

r of p

lann

ed d

oses

.

Prog

ram

mer

not

es: (

a) p

rodu

ce th

e sa

me

tabl

e re

plac

ing

“cis

plat

in”

with

“ca

rbop

latin

” in

the

title

Onc

oMed

Pha

rmac

eutic

als,

Inc.

Stat

istic

al A

naly

sis P

lan

59R

5-00

3 (P

hase

2)

23

MA

R20

17

Conf

iden

tial

Pa

ge 1

01/1

49

APP

EN

DIX

C. F

IGU

RE

SH

EL

LS

Onc

oMed

Pha

rmac

eutic

als,

Inc.

Stat

istic

al A

naly

sis P

lan

59R

5-00

3 (P

hase

2)

23

MA

R20

17

Conf

iden

tial

Pa

ge 1

02/1

49

Onc

oMed

Pha

rmac

eutic

als,

Inc.

Page

1 o

f x

59R

5-00

3 (P

hase

2)

Figu

re 1

4.2.

1.1

O

vera

ll Su

rviv

al

IT

T P

opul

atio

n

Prog

ram

mer

not

es: (

a) re

plac

e “T

reat

men

t A”

with

“Pl

aceb

o”; (

b) re

plac

e “T

reat

men

t B”

with

“Ta

rext

umab

”; (c

) inc

lude

“at

risk

” co

unts

ben

eath

the

x-ax

is (s

ee se

cond

ary

figur

e m

ock

belo

w);

(d

) del

ete

“Tre

atm

ent C

”; (e

) dup

licat

e fig

ure

usin

g pe

r-pr

otoc

ol p

opul

atio

n an

d al

l gen

e-ex

pres

sion

subs

ets o

f the

ITT

popu

latio

n; (f

) dup

licat

e fig

ure

for p

rogr

essi

on-fr

ee su

rviv

al u

sing

the

ITT

popu

latio

n; (f

) dup

licat

e fig

ure

for o

vera

ll su

rviv

al u

sing

the

per-

prot

ocol

pop

ulat

ion

and

all g

ene-

expr

essi

on su

bset

s of t

he IT

T po

pula

tion

Onc

oMed

Pha

rmac

eutic

als,

Inc.

Stat

istic

al A

naly

sis P

lan

59R

5-00

3 (P

hase

2)

23

MA

R20

17

Conf

iden

tial

Pa

ge 1

03/1

49

Seco

ndar

y fig

ure

moc

k sh

owin

g fo

rmat

for “

at ri

sk”

sum

mar

y:

Onc

oMed

Pha

rmac

eutic

als,

Inc.

Stat

istic

al A

naly

sis P

lan

59R

5-00

3 (P

hase

2)

23

MA

R20

17

Conf

iden

tial

Pa

ge 1

04/1

49

Onc

oMed

Pha

rmac

eutic

als,

Inc.

Page

1 o

f x

59R

5-00

3 (P

hase

2)

Figu

re 1

4.2.

4.1

W

ater

fall

Plot

of B

est P

erce

ntag

e C

hang

e fr

om B

asel

ine

Tot

al T

umor

Len

gth

IT

T P

opul

atio

n

Prog

ram

mer

not

es: (

a) re

plac

e “s

cree

ning

” in

the

y-ax

is la

bel w

ith “

Base

line”

; (b)

del

ete

the

foot

note

mar

ker “

[1]”

from

the

y-ax

is la

bel;

(c) d

uplic

ate

figur

e us

ing

per-

prot

ocol

pop

ulat

ion

CR

PRSD

PD

%-Change from Screening [1]

-100-90

-80

-70

-60

-50

-40

-30

-20

-100102030405060708090100

Onc

oMed

Pha

rmac

eutic

als,

Inc.

Stat

istic

al A

naly

sis P

lan

59R

5-00

3 (P

hase

2)

23

MA

R20

17

Conf

iden

tial

Pa

ge 1

05/1

49

Onc

oMed

Pha

rmac

eutic

als,

Inc.

Page

1 o

f x

59R

5-00

3 (P

hase

2)

Figu

re 1

4.3.

4.63

Box

Plo

t of P

ulse

Rat

e by

Vis

it

Safe

ty P

opul

atio

n

Prog

ram

mer

not

es: (

a) re

plac

e “C

ohor

t 1”

with

“Pl

aceb

o”; (

b) re

plac

e “C

ohor

t 2”

with

“Ta

rext

umab

”; (c

) del

ete

“Coh

ort 3

” an

d “C

ohor

t 4”;

(d) d

uplic

ate

figur

e fo

r all

clin

ical

labo

rato

ry, v

ital

sign

and

EC

G p

aram

eter

s (se

e Pl

anne

d Ta

bles

, Fig

ures

and

Lis

tings

[App

endi

x A]

for c

ompl

ete

list);

(e) d

uplic

ate

all f

igur

es fo

r “Bo

x Pl

ot o

f Cha

nge

from

Bas

elin

e Pa

ram

eter

by

Visi

t” –

rem

embe

r to

(i) r

emov

e th

e “B

asel

ine”

mar

ker f

rom

the

x-ax

is a

nd (i

i) re

plac

e th

e y-

axis

labe

l “Pa

ram

eter

(uni

t)” w

ith “

Chan

ge fr

om B

asel

ine

Para

met

er (u

nit)”

Onc

oMed

Pha

rmac

eutic

als,

Inc.

Stat

istic

al A

naly

sis P

lan

59R

5-00

3 (P

hase

2)

23

MA

R20

17

Conf

iden

tial

Pa

ge 1

06/1

49

APP

EN

DIX

D. L

IST

ING

SH

EL

LS

Onc

oMed

Pha

rmac

eutic

als,

Inc.

Stat

istic

al A

naly

sis P

lan

59R

5-00

3 (P

hase

2)

23

MA

R20

17

Conf

iden

tial

Pa

ge 1

07/1

49

Onc

oMed

Pha

rmac

eutic

als,

Inc.

Page

1 o

f x

59R

5-00

3 (P

hase

2)

Lis

ting

16.2

.1.1

Subj

ect D

ispo

sitio

n

Trea

tmen

t G

roup

Subj

ect

ID

ITT

Popu

latio

n Pe

r-Pro

toco

l Po

pula

tion

Safe

ty

Popu

latio

n

Imm

uno-

ge

nici

ty

Popu

latio

n

Phar

mac

o-ki

netic

Po

pula

tion

Trea

tmen

t St

art D

ate

Trea

tmen

t En

d D

ate

Prim

ary

Rea

son

for E

ndin

g St

udy

Trea

tmen

t St

udy

Exit

Dat

e Pr

imar

y R

easo

n fo

r St

udy

Exit

Plac

ebo

| Ta

rext

umab

00

3-xx

x-xx

x Y

| N

Y

| N

Y

| N

Y

| N

Y

| N

dd

mm

myy

yy

ddm

mm

yyyy

Lo

st to

follo

w-u

p |

With

draw

al o

f co

nsen

t/Pat

ient

dec

isio

n |

Dea

th |

Adv

erse

Eve

nt #

xx: A

dver

se

Even

t ter

m |

Dis

ease

Pr

ogre

ssio

n | I

nves

tigat

or

deci

sion

bas

ed o

n pa

tient

's be

st in

tere

st

Stud

y Te

rmin

ated

by

Onc

oMed

| O

ther

: Oth

er

term

ddm

mm

yyyy

D

eath

| Lo

st to

Fol

low

-Up

| St

udy

Term

inat

ed b

y O

ncoM

ed |

With

draw

al

by S

ubje

ct |

Oth

er: O

ther

te

rm

Onc

oMed

Pha

rmac

eutic

als,

Inc.

Stat

istic

al A

naly

sis P

lan

59R

5-00

3 (P

hase

2)

23

MA

R20

17

Conf

iden

tial

Pa

ge 1

08/1

49

Onc

oMed

Pha

rmac

eutic

als,

Inc.

Page

1 o

f x

59R

5-00

3 (P

hase

2)

Lis

ting

16.2

.1.2

Info

rmed

Con

sent

Trea

tmen

t G

roup

Su

bjec

t ID

Info

rmed

C

onse

nt

Dat

e R

ando

miz

atio

n D

ate

Con

sent

ed

to O

ptio

nal

Tum

or

Bio

psy

If Y

es, D

ate

Opt

iona

l Tu

mor

Bio

psy

Con

sent

Dat

e

Con

sent

ed to

O

ptio

nal

Phar

mac

ogen

omic

s B

lood

Sam

ple

If Y

es,

Opt

iona

l Ph

arm

aco-

ge

nom

ics

Blo

od S

ampl

e C

onse

nt D

ate

Con

sent

ed to

D

NA

Te

stin

g on

B

lood

Sa

mpl

e

If Y

es,

DN

A T

estin

g on

Blo

od

Sam

ple

Con

sent

Dat

e

Con

sent

ed to

D

NA

Tes

ting

on T

umor

Ti

ssue

Sa

mpl

e

If Y

es,

DN

A T

estin

g on

Tum

or

Tiss

ue C

onse

nt

Dat

e Pl

aceb

o |

Tare

xtum

ab

003-

xxx-

xxx

ddm

mm

yyyy

dd

mm

myy

yy

Yes

| N

o dd

mm

myy

yy

Yes

| N

o dd

mm

myy

yy

Yes

| N

o dd

mm

myy

yy

Yes

| N

o dd

mm

myy

yy

Onc

oMed

Pha

rmac

eutic

als,

Inc.

Stat

istic

al A

naly

sis P

lan

59R

5-00

3 (P

hase

2)

23

MA

R20

17

Conf

iden

tial

Pa

ge 1

09/1

49

Onc

oMed

Pha

rmac

eutic

als,

Inc.

Page

1 o

f x

59R

5-00

3 (P

hase

2)

Lis

ting

16.2

.2.1

Maj

or P

roto

col D

evia

tions

Tr

eatm

ent

Gro

up

Subj

ect I

D

Prot

ocol

Dev

iatio

n D

escr

iptio

n D

evia

tion

Cod

e

Plac

ebo

| Ta

rext

umab

00

3-xx

x-xx

x D

escr

iptio

n xx

-Dev

iatio

n C

ode

Onc

oMed

Pha

rmac

eutic

als,

Inc.

Stat

istic

al A

naly

sis P

lan

59R

5-00

3 (P

hase

2)

23

MA

R20

17

Conf

iden

tial

Pa

ge 1

10/1

49

Onc

oMed

Pha

rmac

eutic

als,

Inc.

Page

1 o

f x

59R

5-00

3 (P

hase

2)

Lis

ting

16.2

.3.1

Incl

usio

n/E

xclu

sion

Cri

teri

a

Trea

tmen

t G

roup

Su

bjec

t ID

Pr

otoc

ol V

ersi

on D

ate

Did

the

subj

ect m

eet a

ll el

igib

ility

crit

eria

? C

riter

ia T

ype

Crit

erio

n N

umbe

r R

easo

n N

ot M

et

Plac

ebo

| Ta

rext

umab

00

3-xx

x-xx

x dd

mm

myy

yy

Ye

s | N

o In

clus

ion

| Exc

lusi

on |

Non

e xx

R

easo

n

Prog

ram

mer

not

es: (

a) a

ll su

bjec

ts sh

ould

be

liste

d; (b

) Dis

play

“N

one”

for C

rite

ria

Type

as a

ppro

pria

te

Onc

oMed

Pha

rmac

eutic

als,

Inc.

Stat

istic

al A

naly

sis P

lan

59R

5-00

3 (P

hase

2)

23

MA

R20

17

Conf

iden

tial

Pa

ge 1

11/1

49

Onc

oMed

Pha

rmac

eutic

als,

Inc.

Page

1 o

f x

59R

5-00

3 (P

hase

2)

Lis

ting

16.2

.4.1

Dem

ogra

phic

s and

Bas

elin

e C

hara

cter

istic

s Pa

rt 1

of 2

Trea

tmen

t G

roup

Su

bjec

t ID

Dat

e of

Birt

h A

ge

(yea

rs)[1

] Se

x

If Fe

mal

e,

Chi

ld-B

earin

g Po

tent

ial?

R

ace

Ethn

icity

Pl

aceb

o |

Tare

xtum

ab

003-

xxx-

xxx

dd

mm

myy

yy

xx.x

M

ale

| Fe

mal

e Y

es |

No

Am

eric

an In

dian

or

Ala

ska

Nat

ive

| A

sian

| B

lack

or

Afri

can

Am

eric

an |

Nat

ive

Haw

aiia

n or

Oth

er P

acifi

c Is

land

er |

Whi

te

His

pani

c or

La

tino

| N

ot H

isp

anic

or L

atin

o

<s

econ

d pa

rt o

f lis

ting>

Onc

oMed

Pha

rmac

eutic

als,

Inc.

Page

1 o

f x

59R

5-00

3 (P

hase

2)

Lis

ting

16.2

.4.1

Dem

ogra

phic

s and

Bas

elin

e C

hara

cter

istic

s

Part

2 o

f 2

Trea

tmen

t Gro

up

Subj

ect I

D

H

eigh

t (c

m)

Wei

ght

(kg)

Bod

y M

ass

Inde

x [2

]

(mg/

m2 )

ECO

G

Smok

ing

His

tory

If

Ex-S

mok

er o

r Cur

rent

Sm

oker

, nu

mbe

r of p

ack

year

s If

Ex-S

mok

er,

Stop

Dat

e Pl

aceb

o |

Tare

xtum

ab

003-

xxx-

xxx

xx

x xx

.x

x.xx

0

| 1 |

2 N

ever

Sm

oked

| Ex

Sm

oker

| C

urre

nt S

mok

er

xx

ddm

mm

yyyy

[1] A

ge a

t tim

e in

form

ed c

onse

nt w

as si

gned

. [2

] BM

I (kg

/m2 ) =

wei

ght (

kg) /

[hei

ght (

cm)]

2 .

Onc

oMed

Pha

rmac

eutic

als,

Inc.

Stat

istic

al A

naly

sis P

lan

59R

5-00

3 (P

hase

2)

23

MA

R20

17

Conf

iden

tial

Pa

ge 1

12/1

49

Onc

oMed

Pha

rmac

eutic

als,

Inc.

Page

1 o

f x

59R

5-00

3 (P

hase

2)

Lis

ting

16.2

.4.2

Med

ical

/Sur

gica

l His

tory

Trea

tmen

t Gro

up

Subj

ect I

D

Any

pas

t and

/or c

onco

mita

nt d

isea

ses o

r pas

t sur

gerie

s?

Des

crip

tion

of M

edic

al C

ondi

tion/

Even

t O

nset

Dat

e En

d D

ate

Ong

oing

/ R

esol

ved

Plac

ebo

| Ta

rext

umab

00

3-xx

x-xx

x Y

es |

No

Des

crip

tion

ddm

mm

yyyy

dd

mm

myy

yy

Ong

oing

| R

esol

ved

Onc

oMed

Pha

rmac

eutic

als,

Inc.

Stat

istic

al A

naly

sis P

lan

59R

5-00

3 (P

hase

2)

23

MA

R20

17

Conf

iden

tial

Pa

ge 1

13/1

49

Onc

oMed

Pha

rmac

eutic

als,

Inc.

Page

1 o

f x

59R

5-00

3 (P

hase

2)

Lis

ting

16.2

.4.3

Ext

ensi

ve S

mal

l Cel

l Lun

g C

ance

r H

isto

ry

Trea

tmen

t G

roup

Su

bjec

t ID

Dat

e of

D

iagn

osis

(S

tudy

Day

)

Mon

ths

Sinc

e D

iagn

osis

His

tolo

gica

l/ C

ytol

ogic

al

Type

Ana

tom

ical

Lo

catio

n of

Pr

imar

y C

ance

r

Num

ber o

f Si

tes o

f Dis

ease

at

Stu

dy E

ntry

Si

tes o

f Dis

ease

at S

tudy

En

try

Plac

ebo

| Ta

rext

umab

00

3-xx

x-xx

x dd

mm

myy

yy

(xx)

xx

Sm

all C

ell

Onl

y |

Mix

ed T

ype

| Oth

er:

Oth

er te

rm

Rig

ht U

pper

Lun

g |

Rig

ht L

ower

Lun

g |

Mid

dle

of R

ight

Lu

ng |

Left

Upp

er L

ung

| O

ther

: Oth

er te

rm

x B

one

| Bra

in:

Sym

ptom

atic

/ A

sym

ptom

atic

| Pl

eura

| A

dren

al G

land

| Ly

mph

Nod

es: S

peci

fy

Lym

ph N

odes

| O

ther

Nod

es: O

ther

lo

catio

n

Prog

ram

mer

not

es: (

a) fo

r Site

s of D

isea

se a

t Stu

dy E

ntry

, lis

t all

that

app

ly

Onc

oMed

Pha

rmac

eutic

als,

Inc.

Stat

istic

al A

naly

sis P

lan

59R

5-00

3 (P

hase

2)

23

MA

R20

17

Conf

iden

tial

Pa

ge 1

14/1

49

Onc

oMed

Pha

rmac

eutic

als,

Inc.

Page

1 o

f x

59R

5-00

3 (P

hase

2)

Lis

ting

16.2

.4.4

Prio

r Su

rger

y fo

r L

ung

Can

cer

Trea

tmen

t Gro

up

Subj

ect I

D

Prio

r Sur

gery

for

Lung

Can

cer

Surg

ery

Dat

e D

escr

iptio

n of

Sur

gery

Lo

catio

n of

Sur

gery

Pl

aceb

o |

Tare

xtum

ab

003-

xxx-

xxx

Yes

| N

o dd

mm

myy

yy

Des

crip

tion

Loca

tion

Onc

oMed

Pha

rmac

eutic

als,

Inc.

Stat

istic

al A

naly

sis P

lan

59R

5-00

3 (P

hase

2)

23

MA

R20

17

Conf

iden

tial

Pa

ge 1

15/1

49

Onc

oMed

Pha

rmac

eutic

als,

Inc.

Page

1 o

f x

59R

5-00

3 (P

hase

2)

Lis

ting

16.2

.4.5

Prio

r R

adio

ther

apy

for

Lun

g C

ance

r

Trea

tmen

t G

roup

Su

bjec

t ID

Prio

r R

adio

ther

apy

for

Lung

Can

cer

Star

t Dat

e En

d D

ate

Site

of T

reat

men

t To

tal c

GY

Pl

aceb

o |

Tare

xtum

ab

003-

xxx-

xxx

Yes

| N

o dd

mm

myy

yy

ddm

mm

yyyy

Si

te o

f Tre

atm

ent

xx |

Unk

now

n

Onc

oMed

Pha

rmac

eutic

als,

Inc.

Stat

istic

al A

naly

sis P

lan

59R

5-00

3 (P

hase

2)

23

MA

R20

17

Conf

iden

tial

Pa

ge 1

16/1

49

Onc

oMed

Pha

rmac

eutic

als,

Inc.

Page

1 o

f x

59R

5-00

3 (P

hase

2)

Lis

ting

16.2

.4.6

Bas

elin

e G

ene

Exp

ress

ion

Tr

eatm

ent

Gro

up

Subj

ect I

D

Not

ch3

Expr

essi

on

Hes

1 Ex

pres

sion

H

ey1

Expr

essi

on

Hey

2 Ex

pres

sion

H

es6

Expr

essi

on

Plac

ebo

| Ta

rext

umab

00

3-xx

x-xx

x Y

es |

No

Yes

| N

o Y

es |

No

Yes

| N

o Y

es |

No

Onc

oMed

Pha

rmac

eutic

als,

Inc.

Stat

istic

al A

naly

sis P

lan

59R

5-00

3 (P

hase

2)

23

MA

R20

17

Conf

iden

tial

Pa

ge 1

17/1

49

Onc

oMed

Pha

rmac

eutic

als,

Inc.

Page

1 o

f x

59R

5-00

3 (P

hase

2)

Lis

ting

16.2

.4.7

FFPE

Tis

sue

Sam

ple

Part

1 o

f 2

A

rchi

val T

issu

e

Trea

tmen

t Gro

up

Subj

ect I

D

Sam

ple

subm

itted

? B

iops

y D

ate

(Stu

dy D

ay)

Dat

e of

Sub

mis

sion

to

Onc

oMed

(S

tudy

Day

) A

nato

mic

al L

ocat

ion

Loca

tion

Des

crip

tion

Pl

aceb

o |

Tare

xtum

ab

003-

xxx-

xxx

Yes

| N

o dd

mm

myy

yy

(xx)

dd

mm

myy

yy

(xx)

Li

ver |

Lym

ph N

odes

| Pe

riton

eum

| C

hest

Wal

l | A

bdom

en |

Pelv

is |

Bre

ast |

Ski

n |

Kid

ney

| Lun

g |

Oth

er: O

ther

org

an

Des

crip

tion

[1] If

arch

ival

tiss

ue w

as n

ot su

bmitt

ed.

<sec

ond

part

of l

istin

g>

Onc

oMed

Pha

rmac

eutic

als,

Inc.

Page

1 o

f x

59R

5-00

3 (P

hase

2)

Lis

ting

16.2

.4.7

FFPE

Tis

sue

Sam

ple

Part

2 o

f 2

Fr

esh

Tum

or C

ore

Bio

psie

s

Trea

tmen

t Gro

up

Subj

ect I

D

Bio

psie

s Pe

rform

ed?[1

] B

iops

ies D

ate

(Stu

dy D

ay)

Dat

e of

Sub

mis

sion

to

Onc

oMed

(S

tudy

Day

) A

nato

mic

al L

ocat

ion

Loca

tion

Des

crip

tion

Pl

aceb

o |

Tare

xtum

ab

003-

xxx-

xxx

Yes

| N

o dd

mm

myy

yy

(xx)

dd

mm

myy

yy

(xx)

Li

ver |

Lym

ph N

odes

| Pe

riton

eum

| C

hest

Wal

l | A

bdom

en |

Pelv

is |

Bre

ast |

Ski

n |

Kid

ney

| Lun

g |

Oth

er: O

ther

org

an

Des

crip

tion

[1] If

arch

ival

tiss

ue w

as n

ot su

bmitt

ed.

Onc

oMed

Pha

rmac

eutic

als,

Inc.

Stat

istic

al A

naly

sis P

lan

59R

5-00

3 (P

hase

2)

23

MA

R20

17

Conf

iden

tial

Pa

ge 1

18/1

49

Onc

oMed

Pha

rmac

eutic

als,

Inc.

Page

1 o

f x

59R

5-00

3 (P

hase

2)

Lis

ting

16.2

.4.8

Prio

r an

d C

onco

mita

nt M

edic

atio

ns

Trea

tmen

t G

roup

Su

bjec

t ID

Ver

batim

Ter

m //

Pr

efer

red

Nam

e //

A

TC C

lass

[1]

Star

t Dat

e (S

tudy

Day

) En

d D

ate

(Stu

dy D

ay)

R

oute

In

dica

tion

Pl

aceb

o |

Tare

xtum

ab

003-

xxx-

xxx

Ver

batim

Ter

m //

Pr

efer

red

Nam

e //

A

TC C

lass

ddm

mm

yyyy

(x

x)

ddm

mm

yyyy

(x

x) |

Ong

oing

In

hala

tion

| In

tra-a

rteria

l |

Intra

lesi

onal

| In

tram

uscu

lar |

In

traoc

ular

| In

trape

riton

eal |

In

trave

nous

| N

asal

| O

ral |

R

ecta

l |

Subc

utan

eous

| To

pica

l |

Tran

sder

mal

| V

agin

al |

Oth

er: O

ther

te

rm

Med

ical

His

tory

#xx

: MH

te

rm |

Adv

erse

Eve

nt #

xx: A

E te

rm |

Oth

er: O

ther

term

[1

] A

TC C

lass

and

Pre

ferr

ed N

ame

are

code

d us

ing

WH

O D

rug

Dic

tiona

ry E

nhan

ced

(ver

sion

Mar

ch 1

, 201

4).

Onc

oMed

Pha

rmac

eutic

als,

Inc.

Stat

istic

al A

naly

sis P

lan

59R

5-00

3 (P

hase

2)

23

MA

R20

17

Conf

iden

tial

Pa

ge 1

19/1

49

Onc

oMed

Pha

rmac

eutic

als,

Inc.

Page

1 o

f x

59R

5-00

3 (P

hase

2)

Lis

ting

16.2

.4.9

Con

com

itant

Pro

cedu

res

Trea

tmen

t Gro

up

Subj

ect I

D

Any

Con

com

itant

Pr

oced

ures

? Pr

oced

ure

Ana

tom

ical

Lo

catio

n St

art D

ate

(Stu

dy D

ay)

End

Dat

e (S

tudy

Day

)

Indi

catio

n

Plac

ebo

| Ta

rext

umab

00

3-xx

x-xx

x Y

es |

No

Proc

edur

e Lo

catio

n dd

mm

myy

yy (x

x)

ddm

mm

yyyy

(xx)

Med

ical

His

tory

#xx

: MH

term

| A

dver

se E

vent

#xx

: AE

term

| O

ther

: Oth

er te

rm

Onc

oMed

Pha

rmac

eutic

als,

Inc.

Stat

istic

al A

naly

sis P

lan

59R

5-00

3 (P

hase

2)

23

MA

R20

17

Conf

iden

tial

Pa

ge 1

20/1

49

Onc

oMed

Pha

rmac

eutic

als,

Inc.

Page

1 o

f x

59R

5-00

3 (P

hase

2)

Lis

ting

16.2

.5.1

Stud

y D

rug

Infu

sion

Part

1 o

f 3: I

nfus

ion

Adm

inis

trat

ion

Trea

tmen

t G

roup

Su

bjec

t ID

V

isit

Infu

sion

Pe

rform

ed?

If In

fusi

on W

as N

ot

Perfo

rmed

, Sp

ecify

Rea

son

If A

E,

Spec

ify

Dat

e

of In

fusi

on

(Stu

dy D

ay)

Infu

sion

St

art /

St

op T

imes

Inte

nded

D

ose

Per

Prot

ocol

(m

g)

Wha

t Wei

ght

Was

Use

d to

C

alcu

late

Dos

e?

Infu

sion

D

ose

(mg)

Pl

aceb

o |

Tare

xtum

ab

003-

xxx-

xxx

CY

CLE

X

DA

Y X

Y

es |

No

Adv

erse

Eve

nt |

Oth

er:

Oth

er te

rm

AE

term

dd

mm

myy

yy

(xx)

xx

:xx

/ xx

:xx

xx.x

x W

eigh

t at C

urre

nt

Vis

it |

Wei

ght a

t Bas

elin

e |

Oth

er: O

ther

term

xxxx

<

seco

nd p

art o

f lis

ting>

O

ncoM

ed P

harm

aceu

tical

s, In

c.

Pa

ge 1

of x

59

R5-

003

(Pha

se 2

) L

istin

g 16

.2.5

.1

St

udy

Dru

g In

fusi

on

Pa

rt 2

of 3

: Inf

usio

n R

educ

ed o

r D

elay

ed

D

ose

Red

uced

Infu

sion

Del

ayed

Trea

tmen

t G

roup

Su

bjec

t ID

V

isit

Dos

e re

duce

d si

nce

last

in

fusi

on?

Spec

ify R

easo

n If

AE,

Sp

ecify

In

fusi

on

Del

ayed

?

Spec

ify R

easo

n If

AE,

Sp

ecify

Pl

aceb

o |

Tare

xtum

ab

003-

xxx-

xxx

CY

CLE

X D

AY

X

Yes

| N

o A

dver

se E

vent

| O

ther

: Oth

er

term

A

E te

rm

Y

es |

No

Adv

erse

Eve

nt |

Oth

er: O

ther

te

rm

AE

term

<th

ird p

art o

f lis

ting

on n

ext p

age>

O

ncoM

ed P

harm

aceu

tical

s, In

c.

Page

1 o

f x

59R

5-00

3 (P

hase

2)

Lis

ting

16.2

.5.1

Stud

y D

rug

Infu

sion

Part

3 o

f 3: I

nfus

ion

Inte

rrup

ted

or R

esta

rted

Trea

tmen

t G

roup

Su

bjec

t ID

V

isit

Infu

sion

Inte

rrup

ted

R

esta

rt af

ter I

nter

rupt

ion

Com

plet

ed

Afte

r Res

tart

Tota

l Dos

e A

dmin

iste

red

(mg)

In

fusi

on

Inte

rrup

ted?

Spec

ify R

easo

n If

AE,

Sp

ecify

In

fusi

on

Res

tarte

d?

Star

t / S

top

Tim

es

Dos

e (m

g)

Plac

ebo

| Ta

rext

umab

00

3-xx

x-xx

x C

YC

LE X

D

AY

X

Yes

| N

o A

dver

se E

vent

| O

ther

: O

ther

term

A

E te

rm

Y

es |

No

xx:x

x / x

x:xx

xx

xx

Infu

sion

was

co

mpl

eted

| In

fusi

on w

as

inte

rrup

ted

agai

n

xxxx

Onc

oMed

Pha

rmac

eutic

als,

Inc.

Stat

istic

al A

naly

sis P

lan

59R

5-00

3 (P

hase

2)

23

MA

R20

17

Conf

iden

tial

Pa

ge 1

21/1

49

Onc

oMed

Pha

rmac

eutic

als,

Inc.

Page

1 o

f x

59R

5-00

3 (P

hase

2)

Lis

ting

16.2

.5.2

Eto

posi

de In

fusi

on

Pa

rt 1

of 3

: Inf

usio

n A

dmin

istr

atio

n

Trea

tmen

t G

roup

Su

bjec

t ID

V

isit

Infu

sion

Pe

rform

ed?

If In

fusi

on W

as N

ot

Perfo

rmed

, Sp

ecify

Rea

son

If A

E,

Spec

ify

Dat

e

of In

fusi

on

(Stu

dy D

ay)

Infu

sion

St

art /

St

op T

imes

Inte

nded

D

ose

Per

Prot

ocol

(m

g)

Wha

t Wei

ght

Was

Use

d to

C

alcu

late

Dos

e?

BSA

(m

2 )

Act

ual

Dos

e (m

g)

Plac

ebo

| Ta

rext

umab

00

3-xx

x-xx

x C

YC

LE X

D

AY

X

Yes

| N

o A

dver

se E

vent

| O

ther

: O

ther

term

A

E te

rm

ddm

mm

yyyy

(x

x)

xx:x

x /

xx:x

x xx

.xx

Wei

ght a

t Cur

rent

V

isit

| W

eigh

t at B

asel

ine

| O

ther

: Oth

er te

rm

xx

xxxx

<se

cond

par

t of l

istin

g>

Onc

oMed

Pha

rmac

eutic

als,

Inc.

Page

1 o

f x

59R

5-00

3 (P

hase

2)

Lis

ting

16.2

.5.2

Eto

posi

de In

fusi

on

Pa

rt 2

of 3

: Inf

usio

n R

educ

ed o

r D

elay

ed

D

ose

Red

uced

Infu

sion

Del

ayed

Trea

tmen

t G

roup

Su

bjec

t ID

V

isit

Dos

e re

duce

d si

nce

last

in

fusi

on?

Spec

ify R

easo

n If

AE,

Sp

ecify

In

fusi

on

Del

ayed

?

Spec

ify R

easo

n If

AE,

Sp

ecify

Pl

aceb

o |

Tare

xtum

ab

003-

xxx-

xxx

CY

CLE

X D

AY

X

Yes

| N

o A

dver

se E

vent

| O

ther

: Oth

er

term

A

E te

rm

Y

es |

No

Adv

erse

Eve

nt |

Oth

er: O

ther

te

rm

AE

term

<th

ird p

art o

f lis

ting>

O

ncoM

ed P

harm

aceu

tical

s, In

c.

Page

1 o

f x

59R

5-00

3 (P

hase

2)

L

istin

g 16

.2.5

.2

E

topo

side

Infu

sion

Part

3 o

f 3: I

nfus

ion

Inte

rrup

ted

or R

esta

rted

Trea

tmen

t G

roup

Su

bjec

t ID

V

isit

Infu

sion

Inte

rrup

ted

R

esta

rt af

ter I

nter

rupt

ion

Com

plet

ed

Afte

r Res

tart

Tota

l Dos

e A

dmin

iste

red

(mg)

In

fusi

on

Inte

rrup

ted?

Spec

ify R

easo

n If

AE,

Sp

ecify

In

fusi

on

Res

tarte

d?

Star

t / S

top

Tim

es

Dos

e (m

g)

Plac

ebo

| Ta

rext

umab

00

3-xx

x-xx

x C

YC

LE X

D

AY

X

Yes

| N

o A

dver

se E

vent

| O

ther

: O

ther

term

A

E te

rm

Y

es |

No

xx:x

x / x

x:xx

xx

xx

Infu

sion

was

co

mpl

eted

| In

fusi

on w

as

inte

rrup

ted

agai

n

xxxx

Onc

oMed

Pha

rmac

eutic

als,

Inc.

Stat

istic

al A

naly

sis P

lan

59R

5-00

3 (P

hase

2)

23

MA

R20

17

Conf

iden

tial

Pa

ge 1

22/1

49

Onc

oMed

Pha

rmac

eutic

als,

Inc.

Page

1 o

f x

59R

5-00

3 (P

hase

2)

Lis

ting

16.2

.5.3

Plat

inum

The

rapy

Infu

sion

Part

1 o

f 3: I

nfus

ion

Adm

inis

trat

ion

Trea

tmen

t G

roup

Su

bjec

t ID

V

isit

Infu

sion

Pe

rform

ed?

If Y

es, S

peci

fy

ther

apy

If In

fusi

on W

as

Not

Per

form

ed,

Spec

ify R

easo

n If

AE,

Sp

ecify

Dat

e

of In

fusi

on

(Stu

dy D

ay)

Infu

sion

St

art /

St

op

Tim

es

Inte

nded

D

ose

Per

Prot

ocol

Wha

t Wei

ght

Was

Use

d to

C

alcu

late

Dos

e?

BSA

(m

2 )

GFR

( m

L/m

in/

1.73

m2 )

Act

ual

Dos

e (m

g)

Plac

ebo

| Ta

rext

umab

00

3-xx

x-xx

x C

YC

LE X

D

AY

X

Yes

| N

o C

ispl

atin

| C

arbo

plat

in

Adv

erse

Eve

nt |

Oth

er: O

ther

te

rm

AE

term

dd

mm

myy

yy

(xx)

xx

:xx

/ xx

:xx

xx.x

x m

g/m

2 | xx

.xx

mg/

mL-

min

Wei

ght a

t C

urre

nt V

isit

| W

eigh

t at

Bas

elin

e |

Oth

er: O

ther

te

rm

xx

xx

xxxx

<se

cond

par

t of l

istin

g>

Onc

oMed

Pha

rmac

eutic

als,

Inc.

Page

1 o

f x

59R

5-00

3 (P

hase

2)

Lis

ting

16.2

.5.3

Plat

inum

The

rapy

Infu

sion

Part

2 o

f 3: I

nfus

ion

Red

uced

or

Del

ayed

Dos

e R

educ

ed

In

fusi

on D

elay

ed

Trea

tmen

t G

roup

Su

bjec

t ID

V

isit

Dos

e re

duce

d si

nce

last

in

fusi

on?

Spec

ify R

easo

n If

AE,

Sp

ecify

In

fusi

on

Del

ayed

?

Spec

ify R

easo

n If

AE,

Sp

ecify

Pl

aceb

o |

Tare

xtum

ab

003-

xxx-

xxx

CY

CLE

X D

AY

X

Yes

| N

o A

dver

se E

vent

| O

ther

: Oth

er

term

A

E te

rm

Y

es |

No

Adv

erse

Eve

nt |

Oth

er: O

ther

te

rm

AE

term

<th

ird p

art o

f lis

ting>

O

ncoM

ed P

harm

aceu

tical

s, In

c.

Page

1 o

f x

59R

5-00

3 (P

hase

2)

L

istin

g 16

.2.5

.3

Pl

atin

um T

hera

py In

fusi

on

Pa

rt 3

of 3

: Inf

usio

n In

terr

upte

d or

Res

tart

ed

Trea

tmen

t G

roup

Su

bjec

t ID

V

isit

Infu

sion

Inte

rrup

ted

Res

tart

afte

r Int

erru

ptio

n C

ompl

eted

A

fter R

esta

rt

Tota

l Dos

e A

dmin

iste

red

(mg)

Tota

l Pl

anne

d D

ose

(mg)

In

fusi

on

Inte

rrup

ted?

Spec

ify R

easo

n If

AE,

Sp

ecify

In

fusi

on

Res

tarte

d?

Star

t / S

top

Tim

es

Dos

e (m

g)

Plac

ebo

| Ta

rext

umab

00

3-xx

x-xx

x C

YC

LE X

D

AY

X

Yes

| N

o A

dver

se E

vent

| O

ther

: Oth

er te

rm

AE

term

Yes

| N

o xx

:xx

/ xx

:xx

xxxx

In

fusi

on w

as

com

plet

ed |

Infu

sion

was

in

terr

upte

d ag

ain

xxxx

xx

xx

Onc

oMed

Pha

rmac

eutic

als,

Inc.

Stat

istic

al A

naly

sis P

lan

59R

5-00

3 (P

hase

2)

23

MA

R20

17

Conf

iden

tial

Pa

ge 1

23/1

49

Onc

oMed

Pha

rmac

eutic

als,

Inc.

Page

1 o

f x

59R

5-00

3 (P

hase

2)

Lis

ting

16.2

.5.4

Dos

es D

elay

ed, I

nter

rupt

ed, R

educ

ed a

nd N

ot A

dmin

iste

red

Trea

tmen

t Gro

up

Subj

ect I

D

Vis

it D

ate

(Stu

dy D

ay)

Dos

ing

Rea

son

Adv

erse

Eve

nt/O

ther

Rea

son

Plac

ebo

| Ta

rext

umab

00

3-xx

x-xx

x C

YC

LE X

DA

Y X

Y

es |

No

Dos

e D

elay

ed |

D

ose

Inte

rrup

ted

| D

ose

Red

uced

|

Not

Adm

inis

tere

d

Adv

erse

Eve

nt |

Oth

er

Adv

erse

Eve

nt #

xx: A

E te

rm |

Oth

er te

rm

N

ote:

Thi

s lis

ting

is so

rted

by T

reat

men

t, D

osin

g, R

easo

n, a

nd S

ubje

ct.

Onc

oMed

Pha

rmac

eutic

als,

Inc.

Stat

istic

al A

naly

sis P

lan

59R

5-00

3 (P

hase

2)

23

MA

R20

17

Conf

iden

tial

Pa

ge 1

24/1

49

Onc

oMed

Pha

rmac

eutic

als,

Inc.

Page

1 o

f x

59R

5-00

3 (P

hase

2)

Lis

ting

16.2

.5.5

Pre-

dose

, Pos

t-do

se a

nd S

ingl

e PK

Sam

ples

Trea

tmen

t Gro

up

Subj

ect I

D

V

isit

Was

PK

Sam

ple

Dra

wn?

D

raw

Dat

e (S

tudy

Day

) Ti

me

Poin

t D

raw

Tim

e

Plac

ebo

| Ta

rext

umab

00

3-xx

x-xx

x

SCR

EEN

ING

| C

YC

LE X

DA

Y X

Y

es |

No

ddm

mm

yyyy

(x

x)

Pre-

dose

|

Post

-dos

e |

[bla

nk]

xx:x

x

Onc

oMed

Pha

rmac

eutic

als,

Inc.

Stat

istic

al A

naly

sis P

lan

59R

5-00

3 (P

hase

2)

23

MA

R20

17

Conf

iden

tial

Pa

ge 1

25/1

49

Onc

oMed

Pha

rmac

eutic

als,

Inc.

Page

1 o

f x

59R

5-00

3 (P

hase

2)

Lis

ting

16.2

.6.2

Tum

or E

valu

atio

ns –

Tar

get L

esio

ns

Trea

tmen

t G

roup

Su

bjec

t ID

V

isit

Was

ra

diog

raph

ic

eval

uatio

n pe

rform

ed?

Dat

e Pe

rform

ed

(Stu

dy D

ay)

Loca

tion

Num

ber

Loca

tion

Loca

tion

Des

crip

tion

(Pos

ition

with

in O

rgan

) Te

chni

que

Use

d

Thic

knes

s of

slic

e (m

m)[1

]

Long

est

Dia

met

er

(mm

)[2]

Bas

elin

e Su

m o

f Lo

nges

t D

iam

eter

s (m

m)

Vis

it Su

m o

f Lo

nges

t D

iam

eter

s (m

m)

Perc

ent

Cha

nge

from

B

asel

ine

Plac

ebo

| Ta

rext

umab

00

3-xx

x-xx

x SC

REE

NIN

G |

CY

CLE

X D

AY

X

Yes

| N

o dd

mm

myy

yy

(xx)

1

| 2 |

3,

etc.

Pa

ncre

as |

Live

r |

Lym

ph N

odes

| Pe

riton

eum

| C

hest

Wal

l |

Abd

omen

| Pe

lvis

| B

reas

t |

Skin

| K

idne

y |

Lung

| O

ther

: Oth

er

loca

tion

Posi

tion

MR

I |

Con

vent

iona

l CT

| Sp

iral C

T |

PET

CT

| B

one

Scan

| O

ther

: O

ther

te

chni

que

xx.x

xx

.x |

Una

ble

to

Eval

uate

[bla

nk]

[bla

nk]

[bla

nk]

⁞ ⁞

⁞

⁞

Vis

it Su

mm

ary

[bla

nk]

[bla

nk]

[b

lank

] xx

.x

xx.x

| N

A

xx.x

%

[1] If

Spi

ral o

r Con

vent

iona

l CT

Scan

. [2

] If ly

mph

nod

e, sh

ort a

xis m

easu

rem

ent i

s rec

orde

d.

Not

e: C

T =

Com

pute

d To

mog

raph

y, N

A =

Not

App

licab

le.

Prog

ram

mer

not

es: (

a) p

lace

a “

Visi

t Sum

mar

y” ro

w fo

llow

ing

the

last

line

for e

ach

time

poin

t; (b

) lea

ve b

lank

the

cells

for B

asel

ine

Sum

of L

onge

st D

iam

eter

s, Vi

sit S

um o

f Lon

gest

Dia

met

ers,

and

Perc

ent C

hang

e fr

om B

asel

ine

in e

ach

row

exc

ept f

or th

e Vi

sit S

umm

ary

row

des

crib

ed in

not

e (a

)

Onc

oMed

Pha

rmac

eutic

als,

Inc.

Stat

istic

al A

naly

sis P

lan

59R

5-00

3 (P

hase

2)

23

MA

R20

17

Conf

iden

tial

Pa

ge 1

26/1

49

Onc

oMed

Pha

rmac

eutic

als,

Inc.

Page

1 o

f x

59R

5-00

3 (P

hase

2)

Lis

ting

16.2

.6.3

Tum

or E

valu

atio

ns –

Non

-tar

get L

esio

ns

Trea

tmen

t G

roup

Su

bjec

t ID

V

isit

Was

ra

diog

raph

ic

eval

uatio

n pe

rform

ed?

Dat

e Pe

rform

ed

(Stu

dy D

ay)

Loca

tion

Loca

tion

Des

crip

tion

(Pos

ition

with

in O

rgan

) Te

chni

que

Use

d Le

sion

Sta

tus [1

]

Plac

ebo

| Ta

rext

umab

00

3-xx

x-xx

x B

asel

ine

| C

ycle

x

Yes

| N

o dd

mm

myy

yy

(xx)

Pa

ncre

as |

Live

r |

Lym

ph N

odes

| Pe

riton

eum

| C

hest

Wal

l |

Abd

omen

| Pe

lvis

| B

reas

t |

Skin

| K

idne

y |

Lung

| O

ther

: O

ther

loca

tion

Posi

tion

MR

I |

Con

vent

iona

l CT

| Sp

iral C

T |

PET

CT

| B

one

Scan

| O

ther

: Oth

er

tech

niqu

e

CR

| N

on-C

R/N

on-P

D |

PD |

Una

ble

to E

valu

ate

[1

] C

R =

com

plet

e re

spon

se; P

D =

pro

gres

sive

dis

ease

Onc

oMed

Pha

rmac

eutic

als,

Inc.

Stat

istic

al A

naly

sis P

lan

59R

5-00

3 (P

hase

2)

23

MA

R20

17

Conf

iden

tial

Pa

ge 1

28/1

49

Onc

oMed

Pha

rmac

eutic

als,

Inc.

Page

1 o

f x

59R

5-00

3 (P

hase

2)

Lis

ting

16.2

.6.5

Tum

or A

sses

smen

ts (R

EC

IST

Ove

rall

Res

pons

e)

Trea

tmen

t G

roup

Su

bjec

t ID

V

isit

Res

pons

e D

ate

(Stu

dy D

ay)

Targ

et

Lesi

on

Res

pons

e [1

]

Targ

et

Lesi

on

Res

pons

e [1

] N

ew

Lesi

ons

Ove

rall

Res

pons

e A

sses

smen

t [1]

If O

vera

ll R

espo

nse

is

Prog

ress

ive

Dis

ease

, w

as it

non

-rad

iogr

aphi

c cl

inic

al p

rogr

essi

on?

Plac

ebo

| Ta

rext

umab

00

3-xx

x-xx

x SC

REE

NIN

G |

CY

CLE

X

DA

Y X

ddm

mm

yyyy

(x

x)

CR

| PR

| SD

| PD

| U

nabl

e to

Eva

luat

e:

Reas

on |

Not

Ev

alua

ted

No

Lesi

ons a

t Bas

elin

e |

CR

| PR

| SD

| PD

| U

nabl

e to

Eva

luat

e:

Reas

on |

Not

Eva

luat

ed

Yes

| N

o C

R |

PR |

SD |

PD |

PD |

Not

Eva

luat

ed

Yes

| N

o

[1

] CR

= c

ompl

ete

resp

onse

; PR

= p

artia

l res

pons

e; S

D =

stab

le d

isea

se; P

D =

pro

gres

sive

dis

ease

Onc

oMed

Pha

rmac

eutic

als,

Inc.

Stat

istic

al A

naly

sis P

lan

59R

5-00

3 (P

hase

2)

23

MA

R20

17

Conf

iden

tial

Pa

ge 1

29/1

49

Onc

oMed

Pha

rmac

eutic

als,

Inc.

Page

1 o

f x

59R

5-00

3 (P

hase

2)

Lis

ting

16.2

.6.6

Der

ived

Eff

icac

y D

ata

R

ECIS

T v1

.1 A

sses

smen

t

PFS[2

]

OS[3

]

DO

R[4

]

Trea

tmen

t Gro

up

Subj

ect I

D

Bes

t Tum

or R

espo

nse

Obj

ectiv

e R

espo

nse[1

]

Cen

sore

d D

ays

C

enso

red

Day

s

Cen

sore

d D

ays

Plac

ebo

| Ta

rext

umab

00

3-xx

x-xx

x C

R |

PR |

SD |

PD |

NE

Yes

| N

o

Yes

| N

o xx

x

Yes

| N

o xx

x

Yes

| N

o xx

x

Not

e: C

R =

com

plet

e re

spon

se; P

R =

par

tial r

espo

nse;

SD

= st

able

dis

ease

; PD

= p

rogr

essi

ve d

isea

se; N

E =

Not

Eva

luat

ed.

[1] B

est r

espo

nse

of C

R o

r PR

. [2

] Pro

gres

sion

-Fre

e Su

rviv

al (P

FS) =

Dat

e of

Doc

umen

tatio

n of

Dea

th/P

rogr

essi

on –

Ran

dom

izat

ion

Dat

e +

1. S

ubje

cts w

ho h

ad n

ot e

xper

ienc

ed d

eath

or p

rogr

essi

on b

y th

eir l

ast c

onta

ct w

ere

cens

ored

at

the

time

of th

eir l

ast r

adio

grap

hic

resp

onse

ass

essm

ent.

Subj

ects

lack

ing

a ra

diog

raph

ic re

spon

se a

sses

smen

t afte

r ran

dom

izat

ion

who

do

not p

rogr

ess o

r die

hav

e th

eir e

vent

tim

e ce

nsor

ed o

n th

e da

te

of ra

ndom

izat

ion

with

dur

atio

n of

1 d

ay.

[3] O

vera

ll Su

rviv

al (O

S) =

Dat

e of

Doc

umen

tatio

n of

Dea

th –

Ran

dom

izat

ion

Dat

e +

1. S

ubje

cts w

ho h

ad n

ot e

xper

ienc

ed d

eath

by

thei

r las

t con

tact

wer

e ce

nsor

ed a

t the

tim

e. S

ubje

cts l

acki

ng d

ata

afte

r ra

ndom

izat

ion

who

do

not d

ie h

ave

thei

r eve

nt ti

me

cens

ored

on

the

date

of r

ando

miz

atio

n w

ith d

urat

ion

of 1

day

. [4

] Dur

atio

n of

Res

pons

e (D

OR

) = D

ate

of D

ocum

enta

tion

of D

eath

/Pro

gres

sion

– D

ate

of F

irst P

artia

l (PR

) or C

ompl

ete

Res

pons

e (C

R) +

1. P

atie

nts w

ho d

isco

ntin

ue th

e st

udy

with

out d

isea

se

prog

ress

ion

or d

eath

whi

le o

n st

udy

are

cens

ored

on

the

date

of t

he la

st o

n st

udy

tum

or a

sses

smen

t doc

umen

ting

the

abse

nce

of p

rogr

essi

ve d

isea

se. P

atie

nts l

acki

ng a

tum

or a

sses

smen

t afte

r firs

t dos

e w

ho d

o no

t pro

gres

s or d

ie w

hile

on

study

hav

e th

eir e

vent

tim

e ce

nsor

ed o

n th

e da

te o

f firs

t dos

e w

ith d

urat

ion

of 1

day

.

Onc

oMed

Pha

rmac

eutic

als,

Inc.

Stat

istic

al A

naly

sis P

lan

59R

5-00

3 (P

hase

2)

23

MA

R20

17

Conf

iden

tial

Pa

ge 1

30/1

49

Onc

oMed

Pha

rmac

eutic

als,

Inc.

Page

1 o

f x

59R

5-00

3 (P

hase

2)

Lis

ting

16.2

.21

E

nd o

f Tre

atm

ent

Trea

tmen

t G

roup

Su

bjec

t ID

St

udy

Dru

g

Etop

osid

e

Plat

inum

The

rapy

Dat

e of

Las

t Dos

e (S

tudy

Day

) Pr

imar

y R

easo

n fo

r En

ding

Prim

ary

Ass

ocia

ted

AE

Dat

e of

Las

t Dos

e (S

tudy

Day

) Pr

imar

y R

easo

n fo

r En

ding

Prim

ary

Ass

ocia

ted

AE

Dat

e of

Las

t Dos

e (S

tudy

Day

) Pr

imar

y R

easo

n fo

r En

ding

Prim

ary

Ass

ocia

ted

AE

Plac

ebo

| Ta

rext

umab

00

3-xx

x-xx

x dd

mm

myy

yy

(xx)

Lo

st t

o fo

llow

-up

| W

ithdr

awal

of

cons

ent/P

atie

nt

Dec

isio

n |

Dea

th |

Adv

erse

Eve

nt |

Dis

ease

pro

gres

sion

| In

vest

igat

or d

ecis

ion

base

d on

pa

tient

's be

st in

tere

st

| Stud

y Te

rmin

ated

by

Onc

oMed

| O

ther

: Oth

er te

rm

Adv

erse

Ev

ent #

xx:

AE

term

dd

mm

myy

yy

(xx)

Lo

st t

o fo

llow

-up

| W

ithdr

awal

of

cons

ent/P

atie

nt

Dec

isio

n |

Dea

th |

Adv

erse

Eve

nt |

Dis

ease

pr

ogre

ssio

n |

Inve

stig

ator

de

cisi

on b

ased

on

patie

nt's

best

in

tere

st |

Stud

y Te

rmin

ated

by

Onc

oMed

| O

ther

: Oth

er te

rm

Adv

erse

Ev

ent #

xx:

AE

term

dd

mm

myy

yy

(xx)

Lo

st t

o fo

llow

-up

| W

ithdr

awal

of

cons

ent/P

atie

nt

Dec

isio

n |

Dea

th |

Adv

erse

Eve

nt |

Dis

ease

pr

ogre

ssio

n |

Inve

stig

ator

de

cisi

on b

ased

on

patie

nt's

best

in

tere

st |

Stud

y Te

rmin

ated

by

Onc

oMed

| O

ther

: Oth

er te

rm

Adv

erse

Ev

ent #

xx:

AE

term

Onc

oMed

Pha

rmac

eutic

als,

Inc.

Stat

istic

al A

naly

sis P

lan

59R

5-00

3 (P

hase

2)

23

MA

R20

17

Conf

iden

tial

Pa

ge 1

31/1

49

Onc

oMed

Pha

rmac

eutic

als,

Inc.

Page

1 o

f x

59R

5-00

3 (P

hase

2)

Lis

ting

16.2

.7.1

Adv

erse

Eve

nts

Pa

rt 1

of 2

Trea

tmen

t G

roup

Su

bjec

t ID

A

E #

Ver

batim

Ter

m //

M

edD

RA

Pre

ferr

ed T

erm

//

Syst

em O

rgan

Cla

ss

Ons

et D

ate

(Stu

dy D

ay)

End

Dat

e (S

tudy

Day

) O

n-go

ing

Seve

rity

(CTC

AE

V4.

02

Gra

de)

Trea

tmen

t of

Eve

nt

Infu

sion

R

eact

ion

Out

com

e

Cau

sed

Stud

y D

rug

Dis

con-

tin

uatio

n Se

rious

Ev

ent

Serio

us

Even

t Ty

pe

Plac

ebo

|Tar

extu

mab

00

3-xx

x-x

xx

xx

Ver

batim

Ter

m //

M

edD

RA

Pre

ferr

ed T

erm

//

Syst

em O

rgan

Cla

ss

ddm

mm

yyyy

(x

x)

ddm

mm

yyy

y (xx)

Yes

| N

o x

Non

e |

Med

icat

ion

| N

on-D

rug

Trea

tmen

t |

Hos

pita

lizat

ion

Yes

| N

o R

ecov

ered

/Res

olve

d w

ithou

t Se

quel

ae |

Rec

over

ed/R

esol

ved

with

Se

quel

ae |

Not

R

ecov

ered

/Not

Res

olve

d |

Fata

l |

Unk

now

n

Yes

| N

o Y

es |

No

Yes

| N

o

<sec

ond

part

of l

istin

g>

Onc

oMed

Pha

rmac

eutic

als,

Inc.

Page

1 o

f x

59R

5-00

3 (P

hase

2)

Lis

ting

16.2

.7.1

Adv

erse

Eve

nts

Part

2 o

f 2

Trea

tmen

t G

roup

Su

bjec

t ID

A

E #

Rel

atio

nshi

p to

Initi

al A

ctio

n Ta

ken

with

Act

ion

Take

n w

ith

Tare

xtum

ab

Etop

osid

e Pl

atin

um

Ther

apy

Tare

xtum

ab

Etop

osid

e Pl

atin

um

Ther

apy

Tare

xtum

ab

Etop

osid

e Pl

atin

um

Ther

apy

Plac

ebo

| Ta

rext

umab

00

3-xx

x-xx

x xx

R

elat

ed |

Not

Rel

ated

R

elat

ed |

Not

R

elat

ed

Rel

ated

| N

ot

Rel

ated

Non

e |

Dos

e R

educ

ed |

Dos

e D

elay

ed |

Infu

sion

In

terr

upte

d |

With

draw

n |

Not

App

licab

le

Non

e |

Dos

e R

educ

ed |

Dos

e D

elay

ed |

Infu

sion

In

terr

upte

d |

With

draw

n |

Not

App

licab

le

Non

e |

Dos

e R

educ

ed |

Dos

e D

elay

ed |

Infu

sion

In

terr

upte

d |

With

draw

n |

Not

App

licab

le

N

one

| D

ose

Red

uced

| D

ose

Del

ayed

| In

fusi

on

Inte

rrup

ted

| W

ithdr

awn

| N

ot A

pplic

able

Non

e |

Dos

e R

educ

ed |

Dos

e D

elay

ed |

Infu

sion

In

terr

upte

d |

With

draw

n |

Not

App

licab

le

Non

e |

Dos

e R

educ

ed |

Dos

e D

elay

ed |

Infu

sion

In

terr

upte

d |

With

draw

n |

Not

App

licab

le

Prog

ram

mer

not

es: (

a) D

uplic

ate

this

listi

ng to

cre

ate

List

ing

16.2

.7.3

of “

Seri

ous A

dver

se E

vent

s” a

nd L

istin

g 16

.2.7

.4 o

f “Ad

vers

e Ev

ents

Lea

ding

to S

tudy

Dru

g D

iscon

tinua

tion”

Onc

oMed

Pha

rmac

eutic

als,

Inc.

Stat

istic

al A

naly

sis P

lan

59R

5-00

3 (P

hase

2)

23

MA

R20

17

Conf

iden

tial

Pa

ge 1

32/1

49

Onc

oMed

Pha

rmac

eutic

als,

Inc.

Page

1 o

f x

59R

5-00

3 (P

hase

2)

Lis

ting

16.2

.7.2

Dea

ths

Trea

tmen

t Gro

up

Subj

ect I

D

Dat

e of

Dea

th

(Stu

dy D

ay)

Cau

se o

f Dea

th

Prim

ary

Ass

ocia

ted

AE

Plac

ebo

| Ta

rext

umab

00

3-xx

x-xx

x dd

mm

myy

yy (x

x)

Adv

erse

Eve

nt |

Prog

ress

ive

Dis

ease

U

nkno

wn

| O

ther

: Oth

er te

rm

AE

term

Onc

oMed

Pha

rmac

eutic

als,

Inc.

Stat

istic

al A

naly

sis P

lan

59R

5-00

3 (P

hase

2)

23

MA

R20

17

Conf

iden

tial

Pa

ge 1

33/1

49

Onc

oMed

Pha

rmac

eutic

als,

Inc.

Page

1 o

f x

59R

5-00

3 (P

hase

2)

Lis

ting

16.2

.8.1

Hem

atol

ogy

Pa

rt 1

of 2

Trea

tmen

t G

roup

Su

bjec

t ID

V

isit

Sam

ple

colle

cted

?

Col

lect

ion

Dat

e (S

tudy

Day

) C

olle

ctio

n Ti

me

Hem

oglo

bin

(g/d

L)

Hem

atoc

rit

(%)

Plat

elet

s (x

103 /u

L)

RB

C

(x10

6 /uL)

W

BC

(x

103 /u

L)

AN

C

(x10

3 /uL)

Pl

aceb

o |

Tare

xtum

ab

003-

xxx-

xxx

SC

REE

NIN

G |

CY

CLE

X D

AY

X

Yes

| N

o dd

mm

myy

yy

(xx)

xx

:xx

xx.x

L/H

, G1/

G2/

G3/

G4

xx

.x

xx.x

xx

.x

xx.x

xx

.x

Not

e: R

BC

= R

ed B

lood

Cel

ls, W

BC

= W

hite

Blo

od C

ell,

AN

C =

Abs

olut

e N

eutro

phil

Cou

nt, N

D =

Not

Don

e. L

= L

ow, H

= H

igh,

with

resp

ect t

o la

bora

tory

refe

renc

e ra

nges

. Gra

des a

re a

ccor

ding

to

NC

I Com

mon

Ter

min

olog

y C

riter

ia A

dver

se E

vent

s (C

TCA

E) v

ersi

on 4

.03

Prog

ram

min

g no

tes:

Dis

play

L/H

, G1/

G2/

G3/

G4/

G5

for e

ach

lab

test

resu

lt, w

here

app

licab

le.

<se

cond

par

t of l

istin

g>

Onc

oMed

Pha

rmac

eutic

als,

Inc.

Page

1 o

f x

59R

5-00

3 (P

hase

2)

Lis

ting

16.2

.8.1

Hem

atol

ogy

Pa

rt 2

of 2

Trea

tmen

t G

roup

Su

bjec

t ID

V

isit

Sam

ple

colle

cted

?

Col

lect

ion

Dat

e (S

tudy

D

ay)

Col

lect

ion

Tim

e N

eutro

phils

(%

) B

ands

(%

) Ly

mph

ocyt

es

(%)

Eosi

noph

ils

(%)

Mon

ocyt

es

(%)

Bas

ophi

ls

(%)

Plac

ebo

| Ta

rext

umab

00

3-xx

x-xx

x S

CR

EEN

ING

| C

YC

LE X

DA

Y X

Y

es |

No

ddm

mm

yyyy

(xx)

xx

:xx

xx.x

L/H

, G1/

G2/

G3/

G4

xx

.x

xx.x

xx

.x

xx.x

xx

.x

Not

e: R

BC

= R

ed B

lood

Cel

ls, W

BC

= W

hite

Blo

od C

ell,

AN

C =

Abs

olut

e N

eutro

phil

Cou

nt, N

D =

Not

Don

e. L

= L

ow, H

= H

igh,

with

resp

ect t

o la

bora

tory

refe

renc

e ra

nges

. Gra

des a

re a

ccor

ding

to

NC

I Com

mon

Ter

min

olog

y C

riter

ia A

dver

se E

vent

s (C

TCA

E) v

ersi

on 4

.03

Prog

ram

min

g no

tes:

Dis

play

L/H

, G1/

G2/

G3/

G4/

G5

for e

ach

lab

test

resu

lt, w

here

app

licab

le.

Onc

oMed

Pha

rmac

eutic

als,

Inc.

Stat

istic

al A

naly

sis P

lan

59R

5-00

3 (P

hase

2)

23

MA

R20

17

Conf

iden

tial

Pa

ge 1

34/1

49

Onc

oMed

Pha

rmac

eutic

als,

Inc.

Page

1 o

f x

59R

5-00

3 (P

hase

2)

Lis

ting

16.2

.8.2

PT/I

NR

and

aPT

T

Trea

tmen

t G

roup

Su

bjec

t ID

V

isit

Sam

ple

colle

cted

?

Col

lect

ion

Dat

e (S

tudy

Day

) C

olle

ctio

n Ti

me

Prot

hrom

bin

Tim

e (P

T)

(sec

)

Inte

rnat

iona

l N

orm

aliz

ed

Rat

io (I

NR

)

Act

ivat

ed P

artia

l Th

rom

bopl

astin

Ti

me

(aPT

T)

(sec

)

Plac

ebo

| Ta

rext

umab

00

3-xx

x-xx

x S

CR

EEN

ING

| C

YC

LE X

DA

Y X

Y

es |

No

ddm

mm

yyyy

(x

x)

xx:x

x xx

.xL/

H, G

1/G

2/G

3/G

4

xx

.x

xx.x

N

ote:

ND

= N

ot D

one.

L =

Low

, H =

Hig

h, w

ith re

spec

t to

labo

rato

ry re

fere

nce

rang

es. G

rade

s are

acc

ordi

ng to

NC

I Com

mon

Ter

min

olog

y C

riter

ia A

dver

se E

vent

s (C

TCA

E) v

ersi

on 4

.03

Prog

ram

min

g no

tes:

Dis

play

L/H

, G1/

G2/

G3/

G4

for e

ach

lab

test

resu

lt, w

here

app

licab

le.

Onc

oMed

Pha

rmac

eutic

als,

Inc.

Stat

istic

al A

naly

sis P

lan

59R

5-00

3 (P

hase

2)

23

MA

R20

17

Conf

iden

tial

Pa

ge 1

35/1

49

Onc

oMed

Pha

rmac

eutic

als,

Inc.

Page

1 o

f x

59R

5-00

3 (P

hase

2)

Lis

ting

16.2

.8.3

Seru

m C

hem

istr

y

Part

1 o

f 2

Trea

tmen

t G

roup

Su

bjec

t ID

V

isit

Sam

ple

colle

cted

?

Col

lect

ion

Dat

e (S

tudy

Day

) C

olle

ctio

n Ti

me

Fast

ing

for a

t lea

st

6 ho

urs?

A

lbum

in

(g/d

L)

Alk

alin

e Ph

osph

atas

e (U

/L)

Tota

l B

iliru

bin

(mg/

dL)

Dire

ct

Bili

rubi

n (m

g/dL

) B

icar

bona

te

(mEq

/L)

Blo

od

Ure

a N

itrog

en

(mg/

dL)

Cal

cium

(m

g/dL

) C

hlor

ide

(mEq

/L)

Plac

ebo

| Ta

rext

umab

00

3-xx

x-xx

x S

CR

EEN

ING

| C

YC

LE X

DA

Y X

Y

es |

No

ddm

mm

yyyy

(x

x)

xx:x

x Y

es |

No

xx.x

L/H

,

G1/

G2/

G3/

G4

xx.x

xx

.x

xx.x

xx

.x

xx.x

xx

.x

xx.x

N

ote:

LD

H =

Lac

tic D

ehyd

roge

nase

, ND

= N

ot D

one.

L =

Low

, H =

Hig

h, w

ith re

spec

t to

labo

rato

ry re

fere

nce

rang

es. G

rade

s are

acc

ordi

ng to

NC

I Com

mon

Ter

min

olog

y C

riter

ia A

dver

se E

vent

s (C

TCA

E) v

ersi

on 4

.03

Prog

ram

min

g no

tes:

Dis

play

L/H

, G1/

G2/

G3/

G4/

G5

for e

ach

lab

test

resu

lt, w

here

app

licab

le.

<se

cond

par

t of l

istin

g>

Onc

oMed

Pha

rmac

eutic

als,

Inc.

Page

1 o

f x

59R

5-00

3 (P

hase

2)

Lis

ting

16.2

.8.3

Seru

m C

hem

istr

y

Part

2 o

f 2

Trea

tmen

t G

roup

Su

bjec

t ID

V

isit

Sam

ple

colle

cted

?

Col

lect

ion

Dat

e (S

tudy

Day

) C

olle

ctio

n Ti

me

Fast

ing

for a

t le

ast 6

ho

urs?

Cre

atin

-in

e (m

g/dL

)

Blo

od

Glu

cose

(m

g/dL

) LD

H

(U/L

)

Mag

nes-

ium

(m

g/dL

)

Phos

ph-

orus

(m

g/dL

) Po

tass

ium

(m

Eq/L

)

Tota

l Pr

otei

n (g

/dL)

AST

(S

GO

T)

(U/L

)

ALT

(S

GPT

) (U

/L)

Sodi

um

(mEq

/L)

Plac

ebo

| Ta

rext

umab

00

3-xx

x-xx

x S

CR

EEN

ING

| C

YC

LE X

D

AY

X

Yes

| N

o dd

mm

myy

yy

(xx)

xx

:xx

Yes

| N

o xx

.xL/

H,

G1/

G2/

G3/

G4

xx.x

xx

.x

xx.x

xx

.x

xx.x

xx

.x

xx.x

xx

.x

Not

e: L

DH

= L

actic

Deh

ydro

gena

se, N

D =

Not

Don

e. L

= L

ow, H

= H

igh,

with

resp

ect t

o la

bora

tory

refe

renc

e ra

nges

. Gra

des a

re a

ccor

ding

to N

CI C

omm

on T

erm

inol

ogy

Crit

eria

Adv

erse

Eve

nts

(CTC

AE)

ver

sion

4.0

3

Prog

ram

min

g no

tes:

Dis

play

L/H

, G1/

G2/

G3/

G4/

G5

for e

ach

lab

test

resu

lt, w

here

app

licab

le.

Onc

oMed

Pha

rmac

eutic

als,

Inc.

Stat

istic

al A

naly

sis P

lan

59R

5-00

3 (P

hase

2)

23

MA

R20

17

Conf

iden

tial

Pa

ge 1

36/1

49

Onc

oMed

Pha

rmac

eutic

als,

Inc.

Page

1 o

f x

59R

5-00

3 (P

hase

2)

Lis

ting

16.2

.8.4

Uri

naly

sis

Pa

rt 1

of 2

Trea

tmen

t G

roup

Su

bjec

t ID

Vis

it Sa

mpl

e co

llect

ed?

Col

lect

ion

Dat

e (S

tudy

Day

)

Col

lect

- io

n Ti

me

Prot

ein

Glu

cose

K

eton

es

Blo

od

Bili

rubi

n pH

Sp

ecifi

c G

ravi

ty

Plac

ebo

| Ta

rext

umab

00

3-xx

x-xx

x

SCR

EEN

ING

| C

YC

LE 1

DA

Y 1

Y

es |

No

ddm

mm

yyyy

(x

x)

xx:x

x N

egat

ive

| Po

sitiv

e:

Trac

e/

1+/

2+/

3+/

4+/

Unk

now

n |

Not

Don

e

Neg

ativ

e |

Posi

tive

| Not

D

one

Neg

ativ

e |

Posi

tive

| Not

D

one

Neg

ativ

e |

Posi

tive

| Not

D

one

Neg

ativ

e |

Posi

tive

| Not

D

one

x.x

x.xx

<se

cond

par

t of l

istin

g>

Onc

oMed

Pha

rmac

eutic

als,

Inc.

Page

1 o

f x

59R

5-00

3 (P

hase

2)

Lis

ting

16.2

.8.4

Uri

naly

sis

Pa

rt 2

of 2

Trea

tmen

t G

roup

Su

bjec

t ID

Vis

it Sa

mpl

e co

llect

ed?

Col

lect

ion

Dat

e (S

tudy

Day

) C

olle

ctio

n Ti

me

Mic

rosc

opic

Ex

am

Perfo

rmed

? B

acte

ria

Cas

ts

Cry

stal

s R

BC

(c

ells

/hpf

) W

BC

(c

ells

/hpf

) O

ther

te

st

Res

ult

(uni

ts)

Ref

eren

ce

Ran

ge

Plac

ebo

| Ta

rext

umab

00

3-xx

x-xx

x

SCR

EEN

ING

| C

YC

LE 1

DA

Y

1

Yes

| N

o dd

mm

myy

yy

(xx)

xx

:xx

Yes

| N

o A

bsen

t |

Pres

ent |

N

ot D

one

Abs

ent |

Pr

esen

t |

Not

D

one

Abs

ent |

Pr

esen

t |

Not

Don

e

xx

xx

x.xx

xx

un

its

xx-x

x

Onc

oMed

Pha

rmac

eutic

als,

Inc.

Stat

istic

al A

naly

sis P

lan

59R

5-00

3 (P

hase

2)

23

MA

R20

17

Conf

iden

tial

Pa

ge 1

37/1

49

Onc

oMed

Pha

rmac

eutic

als,

Inc.

Page

1 o

f x

59R

5-00

3 (P

hase

2)

Lis

ting

16.2

.8.5

Vita

l Sig

ns

Trea

tmen

t G

roup

Su

bjec

t ID

Vis

it V

ital S

igns

M

easu

red?

D

ate

(Stu

dy

Day

) Ti

me

Tem

pera

ture

(°

C)

Puls

e R

ate

(bea

st/m

in)

Res

pira

tory

Rat

e (b

eats

/min

)

Blo

od P

ress

ure

(Sys

tolic

/ D

iast

olic

) (m

mH

g)

Hei

ght

(cm

) W

eigh

t (k

g)

Plac

ebo

| Ta

rext

umab

00

3-xx

x-xx

x

SCR

EEN

ING

| C

YC

LE X

DA

Y X

Y

es |

No

ddm

mm

yyyy

xx

:xx

xx.x

xx

xx

xx

x/xx

xx

x.x

xx.x

Onc

oMed

Pha

rmac

eutic

als,

Inc.

Stat

istic

al A

naly

sis P

lan

59R

5-00

3 (P

hase

2)

23

MA

R20

17

Conf

iden

tial

Pa

ge 1

38/1

49

Onc

oMed

Pha

rmac

eutic

als,

Inc.

Page

1 o

f x

59R

5-00

3 (P

hase

2)

Lis

ting

16.2

.8.6

EC

OG

Per

form

ance

Sta

tus

Trea

tmen

t G

roup

Su

bjec

t ID

V

isit

ECO

G

Ass

essm

ent

Perfo

rmed

?

Ass

essm

ent

Dat

e (S

tudy

Day

) Sc

ore[1

]

Plac

ebo

| Ta

rext

umab

00

3-xx

x-xx

x SC

REE

NIN

G |

CY

CLE

X

DA

Y X

Y

es |

No

ddm

mm

yyyy

(x

x)

x

[1] 0

= F

ully

act

ive,

abl

e to

car

ry o

n al

l pre

-dis

ease

per

form

ance

with

out r

estri

ctio

n; 1

= R

estri

cted

in p

hysi

cally

stre

nuou

s act

ivity

, but

am

bula

tory

and

abl

e to

car

ry o

ut w

ork

of a

lig

ht o

r sed

enta

ry n

atur

e (e

.g.,

light

hou

sew

ork,

off

ice

wor

k; 2

= A

mbu

lato

ry a

nd c

apab

le o

f all

self

-car

e, b

ut u

nabl

e to

car

ry o

ut a

ny w

ork

activ

ities

. Up

and

abou

t mor

e th

an 5

0%

of w

akin

g ho

ur; 3

= C

apab

le o

f onl

y lim

ited

self-

care

, con

fined

to b

ed o

r cha

ir m

ore

than

50%

of w

akin

g ho

ur; 4

= C

ompl

etel

y di

sabl

ed. C

anno

t car

ry o

n an

y se

lf-ca

re. T

otal

ly

conf

ined

to b

ed o

r cha

ir; 5

= D

ead.

Onc

oMed

Pha

rmac

eutic

als,

Inc.

Stat

istic

al A

naly

sis P

lan

59R

5-00

3 (P

hase

2)

23

MA

R20

17

Conf

iden

tial

Pa

ge 1

39/1

49

Onc

oMed

Pha

rmac

eutic

als,

Inc.

Page

1 o

f x

59R

5-00

3 (P

hase

2)

Lis

ting

16.2

.8.7

12-L

ead

EC

G

Pa

rt 1

of 2

Trea

tmen

t Gro

up

Subj

ect I

D

Vis

it W

as E

CG

Pe

rform

ed?

Dat

e of

A

sses

smen

t (S

tudy

Day

) PR

Inte

rval

(m

sec)

Q

RS

Dur

atio

n (m

sec)

QTc

In

terv

al

(mse

c)

QTc

Inte

rval

Fo

rmul

a

Plac

ebo

| Ta

rext

umab

00

3-xx

x-xx

x SC

REE

NIN

G |

CY

CLE

X D

AY

X

Yes

| N

o dd

mm

myy

yy

(xx)

xx

x xx

x

xxx

Baz

ett |

Fr

ider

icia

Not

e: M

H =

Med

ical

His

tory

<se

cond

par

t of l

istin

g>

Onc

oMed

Pha

rmac

eutic

als,

Inc.

Page

1 o

f x

59R

5-00

3 (P

hase

2)

Lis

ting

16.2

.8.7

12-L

ead

EC

G

Pa

rt 2

of 2

Trea

tmen

t Gro

up

Subj

ect I

D

V

isit

Was

EC

G

Perfo

rmed

?

Dat

e of

A

sses

smen

t (S

tudy

Day

) In

terp

reta

tion

If A

bnor

mal

, D

escr

ibe

Abn

orm

ality

If A

bnor

mal

, C

linic

ally

Si

gnifi

cant

?

Prim

ary

Ass

ocia

ted

AE

Prim

ary

Ass

ocia

ted

MH

Plac

ebo

| Ta

rext

umab

00

3-xx

x-xx

x

SCR

EEN

ING

| C

YC

LE X

DA

Y X

Y

es |

No

ddm

mm

yyyy

(x

x)

Nor

mal

| A

bnor

mal

D

escr

iptio

n

Yes

| N

o A

E te

rm

MH

term

N

ote:

MH

= M

edic

al H

isto

ry

Onc

oMed

Pha

rmac

eutic

als,

Inc.

Stat

istic

al A

naly

sis P

lan

59R

5-00

3 (P

hase

2)

23

MA

R20

17

Conf

iden

tial

Pa

ge 1

40/1

49

Onc

oMed

Pha

rmac

eutic

als,

Inc.

Page

1 o

f x

59R

5-00

3 (P

hase

2)

Lis

ting

16.2

.8.8

Phys

ical

Exa

min

atio

n

Trea

tmen

t Gro

up

Subj

ect I

D

V

isit

Was

Phy

sica

l Exa

m

Perfo

rmed

?

Dat

e of

Ex

am

(Stu

dy D

ay)

Abn

orm

al

Find

ings

?

If A

bnor

mal

, C

linic

ally

Si

gnifi

cant

?

If Y

es,

Prim

ary

MH

If Y

es,

Prim

ary

AE

If N

o,

Des

crip

tion

of N

on-

Clin

ical

ly

Sign

ifica

nt A

bnor

mal

ity

Plac

ebo

| Ta

rext

umab

00

3-xx

x-xx

x

SCR

EEN

ING

| C

YC

LE X

DA

Y X

Y

es |

No

ddm

mm

yyyy

(x

x)

Yes

| N

o Y

es |

No

MH

term

A

E te

rm

Des

crip

tion

N

ote:

MH

= M

edic

al H

isto

ry

Onc

oMed

Pha

rmac

eutic

als,

Inc.

Stat

istic

al A

naly

sis P

lan

59R

5-00

3 (P

hase

2)

23

MA

R20

17

Conf

iden

tial

Pa

ge 1

41/1

49

Onc

oMed

Pha

rmac

eutic

als,

Inc.

Page

1 o

f x

59R

5-00

3 (P

hase

2)

Lis

ting

16.2

.8.9

Opt

iona

l Blo

od fo

r Ph

arm

acog

enom

ics

Trea

tmen

t Gro

up

Subj

ect I

D

V

isit

Was

opt

iona

l blo

od sa

mpl

e co

llect

ed fo

r ph

arm

acog

enom

ics?

PG

Blo

od D

ate

of C

olle

ctio

n (S

tudy

Day

) Pl

aceb

o |

Tare

xtum

ab

003-

xxx-

xxx

SC

REE

NIN

G |

CY

CLE

X D

AY

X

Yes

| N

o dd

mm

myy

yy

(xx)

Onc

oMed

Pha

rmac

eutic

als,

Inc.

Stat

istic

al A

naly

sis P

lan

59R

5-00

3 (P

hase

2)

23

MA

R20

17

Conf

iden

tial

Pa

ge 1

42/1

49

Onc

oMed

Pha

rmac

eutic

als,

Inc.

Page

1 o

f x

59R

5-00

3 (P

hase

2)

Lis

ting

16.2

.8.1

0

CA

19-

9 T

umor

Mar

ker

Trea

tmen

t Gro

up

Subj

ect I

D

V

isit

Was

the

CA

19-9

Tum

or M

arke

r Sa

mpl

e C

olle

cted

? C

olle

ctio

n D

ate

(Stu

dy D

ay)

Res

ult (

Uni

ts)

Plac

ebo

| Ta

rext

umab

00

3-xx

x-xx

x

SCR

EEN

ING

| C

YC

LE X

DA

Y X

Y

es |

No

ddm

mm

yyyy

(x

x)

xxxx

x.x

units

Onc

oMed

Pha

rmac

eutic

als,

Inc.

Stat

istic

al A

naly

sis P

lan

59R

5-00

3 (P

hase

2)

23

MA

R20

17

Conf

iden

tial

Pa

ge 1

43/1

49

Onc

oMed

Pha

rmac

eutic

als,

Inc.

Page

1 o

f x

59R

5-00

3 (P

hase

2)

Lis

ting

16.2

.8.1

1

Ant

i-Tar

extu

mab

Ant

ibod

ies

Trea

tmen

t Gro

up

Subj

ect I

D

V

isit

Was

the

Ant

i-Tar

extu

mab

Ant

ibod

y Sa

mpl

e C

olle

cted

? C

olle

ctio

n D

ate

(Stu

dy D

ay)

Plac

ebo

| Ta

rext

umab

00

3-xx

x-xx

x

SCR

EEN

ING

| C

YC

LE X

DA

Y X

Y

es |

No

ddm

mm

yyyy

(x

x)

Onc

oMed

Pha

rmac

eutic

als,

Inc.

Stat

istic

al A

naly

sis P

lan

59R

5-00

3 (P

hase

2)

23

MA

R20

17

Conf

iden

tial

Pa

ge 1

44/1

49

Onc

oMed

Pha

rmac

eutic

als,

Inc.

Page

1 o

f x

59R

5-00

3 (P

hase

2)

Lis

ting

16.2

.8.1

2

Blo

od fo

r B

iom

arke

rs

Trea

tmen

t G

roup

Su

bjec

t ID

V

isit

Was

Blo

od S

ampl

e fo

r Pl

asm

a B

iom

arke

rs

Col

lect

ed?

Blo

od S

ampl

e fo

r Pl

asm

a B

iom

arke

rs

Col

lect

ion

Dat

e (S

tudy

Day

)

Was

Blo

od S

ampl

e fo

r m

RN

A B

iom

arke

rs

Col

lect

ed?

Blo

od S

ampl

e fo

r m

RN

A B

iom

arke

rs

Col

lect

ion

Dat

e (S

tudy

Day

)

Was

Blo

od

Sam

ple

for C

TCs

Col

lect

ed?

Blo

od S

ampl

e fo

r C

TCs C

olle

ctio

n D

ate

(Stu

dy D

ay)

Plac

ebo

| Ta

rext

umab

00

3-xx

x-xx

x SC

REE

NIN

G |

CY

CLE

X D

AY

X

Yes

| N

o dd

mm

myy

yy

(xx)

Y

es |

No

ddm

mm

yyyy

(x

x)

Yes

| N

o dd

mm

myy

yy

(xx)

Onc

oMed

Pha

rmac

eutic

als,

Inc.

Stat

istic

al A

naly

sis P

lan

59R

5-00

3 (P

hase

2)

23

MA

R20

17

Conf

iden

tial

Pa

ge 1

45/1

49

Onc

oMed

Pha

rmac

eutic

als,

Inc.

Page

1 o

f x

59R

5-00

3 (P

hase

2)

Lis

ting

16.2

.8.1

3

Seru

m P

regn

ancy

Tes

t

Trea

tmen

t Gro

up

Subj

ect I

D

Vis

it W

as th

e Pr

egna

ncy

Test

per

form

ed?

If N

o, S

peci

fy R

easo

n D

ate

of A

sses

smen

t (S

tudy

Day

)

Res

ult

Plac

ebo

| Ta

rext

umab

00

3-xx

x-xx

x SC

REE

NIN

G |

UN

SCH

EDU

LED

Y

es |

No

Prio

r Hys

tere

ctom

y |

Oth

er R

easo

n:

ddm

mm

yyyy

(x

x)

Posi

tive

| Neg

ativ

e

Onc

oMed

Pha

rmac

eutic

als,

Inc.

Stat

istic

al A

naly

sis P

lan

59R

5-00

3 (P

hase

2)

23

MA

R20

17

Conf

iden

tial

Pa

ge 1

46/1

49

Onc

oMed

Pha

rmac

eutic

als,

Inc.

Page

1 o

f x

59R

5-00

3 (P

hase

2)

Lis

ting

16.2

.8.1

4

Opt

iona

l Tum

or C

ore

Bio

psy

Trea

tmen

t Gro

up

Subj

ect I

D

Vis

it W

as a

n O

ptio

nal T

umor

Cor

e B

iops

y Sa

mpl

e C

olle

cted

? D

ate

of C

olle

ctio

n (S

tudy

Day

) Ti

me

of C

olle

ctio

n Lo

catio

n Lo

catio

n D

escr

iptio

n (P

ositi

on w

ithin

Org

an)

Plac

ebo

| Ta

rext

umab

00

3-xx

x-xx

x SC

REE

NIN

G |

CY

CLE

X D

AY

X

Yes

| N

o dd

mm

myy

yy

(xx)

xx

:xx

Panc

reas

| Li

ver |

Ly

mph

| N

odes

| Pe

riton

eum

| C

hest

Wal

l |

Abd

omen

| Pe

lvis

| B

reas

t |

Skin

| K

idne

y |

Lung

| O

ther

: Oth

er

orga

n

Des

crip

tion

Onc

oMed

Pha

rmac

eutic

als,

Inc.

Stat

istic

al A

naly

sis P

lan

59R

5-00

3 (P

hase

2)

23

MA

R20

17

Conf

iden

tial

Pa

ge 1

47/1

49

Onc

oMed

Pha

rmac

eutic

als,

Inc.

Page

1 o

f x

59R

5-00

3 (P

hase

2)

Lis

ting

16.2

.8.1

5

On

Stud

y PC

I or

WB

RT

(PC

I)

Trea

tmen

t G

roup

Su

bjec

t ID

V

isit

Prop

hyla

ctic

Cra

nial

Irra

diat

ion

(PC

I)

Who

le B

rain

Rad

iatio

n [W

BR

T (P

CI)]

A

dmin

iste

red

durin

g st

udy?

To

tal

cGY

St

art D

ate

(Stu

dy D

ay)

Stop

Dat

e (S

tudy

Day

)

Adm

inis

tere

d du

ring

stud

y?

Tota

l cG

Y

Star

t Dat

e (S

tudy

Day

) St

op D

ate

(Stu

dy D

ay)

Plac

ebo

| Ta

rext

umab

00

3-xx

x-xx

x SC

REE

NIN

G |

CY

CLE

X

DA

Y X

Yes

| N

o xx

| U

nkno

wn

ddm

mm

yyyy

(x

x)

ddm

mm

yyyy

(x

x)

Y

es |

No

xx |

Unk

now

n dd

mm

myy

yy

(xx)

dd

mm

myy

yy

(xx)

Onc

oMed

Pha

rmac

eutic

als,

Inc.

Stat

istic

al A

naly

sis P

lan

59R

5-00

3 (P

hase

2)

23

MA

R20

17

Conf

iden

tial

Pa

ge 1

48/1

49

Onc

oMed

Pha

rmac

eutic

als,

Inc.

Page

1 o

f x

59R

5-00

3 (P

hase

2)

Lis

ting

16.2

.8.1

6

Follo

w-U

p A

fter

Dis

cont

inua

tion

of S

tudy

Tre

atm

ent

Trea

tmen

t Gro

up

Subj

ect I

D

Vis

it W

as a

Sur

viva

l Fol

low

-Up

Don

e?

Dat

e of

Su

rviv

al A

sses

smen

t (S

tudy

Day

) Su

bjec

t Sta

tus

Last

Kno

wn

Surv

ival

Dat

e (S

tudy

Day

)

Plac

ebo

| Ta

rext

umab

00

3-xx

x-xx

x X

MO

NTH

SU

RV

IVA

L FO

LLO

W-U

P Y

es |

No

ddm

mm

yyyy

(xx)

A

live

| D

ead

| Lo

st to

Fol

low

-Up

ddm

mm

yyyy

(xx)

Onc

oMed

Pha

rmac

eutic

als,

Inc.

Stat

istic

al A

naly

sis P

lan

59R

5-00

3 (P

hase

2)

23

MA

R20

17

Conf

iden

tial

Pa

ge 1

49/1

49

Onc

oMed

Pha

rmac

eutic

als,

Inc.

Page

1 o

f x

59R

5-00

3 (P

hase

2)

Lis

ting

16.2

.17

T

reat

men

ts a

nd P

roce

dure

s for

Ext

ensi

ve S

mal

l Lun

g C

ance

r D

urin

g Fo

llow

-Up

Peri

od

Part

1 o

f 3: S

urge

ry

Trea

tmen

t Gro

up

Subj

ect I

D

Vis

it

Any

surg

erie

s for

the

treat

men

t of l

ung

canc

er

durin

g fo

llow

-up

perio

d?

Surg

ery

Des

crip

tion

Loca

tion

Surg

ery

Dat

e (S

tudy

Day

)

Plac

ebo

| Ta

rext

umab

00

3-xx

x-xx

x X

MO

NTH

SU

RV

IVA

L FO

LLO

W-U

P Y

es |

No

Des

crip

tion

Loca

tion

ddm

mm

yyyy

(xx)

<se

cond

par

t of l

istin

g>

Onc

oMed

Pha

rmac

eutic

als,

Inc.

Page

1 o

f x

59R

5-00

3 (P

hase

2)

Lis

ting

16.2

.17

T

reat

men

ts a

nd P

roce

dure

s for

Ext

ensi

ve S

mal

l Lun

g C

ance

r D

urin

g Fo

llow

-Up

Peri

od

Part

2 o

f 3: R

adio

ther

apy

Trea

tmen

t Gro

up

Subj

ect I

D

Vis

it

Any

radi

othe

rapy

fo

r the

trea

tmen

t of

lung

can

cer d

urin

g fo

llow

-up

perio

d?

Site

of T

reat

men

t To

tal c

GY

St

art D

ate

(Stu

dy D

ay)

Stop

Dat

e (S

tudy

Day

) Sy

stem

ic T

hera

py?

Plac

ebo

| Ta

rext

umab

00

3-xx

x-xx

x X

MO

NTH

SU

RV

IVA

L FO

LLO

W-U

P Y

es |

No

Site

xx

| U

nkno

wn

ddm

mm

yyyy

(xx)

dd

mm

myy

yy (x

x)

Yes

| N

o

<

third

par

t of l

istin

g>

Onc

oMed

Pha

rmac

eutic

als,

Inc.

Page

1 o

f x

59R

5-00

3 (P

hase

2)

Lis

ting

16.2

.17

T

reat

men

ts a

nd P

roce

dure

s for

Ext

ensi

ve S

mal

l Lun

g C

ance

r D

urin

g Fo

llow

-Up

Peri

od

Part

3 o

f 3: S

yste

mic

The

rapy

Trea

tmen

t Gro

up

Subj

ect I

D

Vis

it

Any

syst

emic

ther

apy

for t

he

treat

men

t of l

ung

canc

er

durin

g fo

llow

-up

perio

d?

Reg

imen

St

art D

ate

(Stu

dy D

ay)

End

Dat

e (S

tudy

Day

) Pl

aceb

o |

Tare

xtum

ab

003-

xxx-

xxx

X M

ON

TH S

UR

VIV

AL

FOLL

OW

-UP

Yes

| N

o R

egim

en

ddm

mm

yyyy

(xx)

dd

mm

myy

yy (x

x)

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