disclosure - oncology leanring network · presentation 1,2) naïve t cell reactivation of t cells...

Kei Muro, MD.

[email protected]

Department of Clinical Oncology

Aichi Cancer Center Hospital

Nagoya, JAPAN

Where Are We with Check-Point Inhibitors

in Gastric Cancer?

21 June 2018, Barcelona

Session VII: Metastatic Gastric Cancer

Disclosure

Research Funding:

Gilead Sciences, Merck Serono, MSD, Daiichi Sankyo, Sanofi,

Ono, Shionogi, Medisience Planning, Pfizer, and Kyowa Hakko Kirin

Lecture Fee:Chugai, Eli Lilly, Takeda, Ono, Taiho, and Bayer

Kei Muro, MD.

Hayakawa Y, et al. Nature Reviews Cancer 16: 305-318, 2016

Molecular Subtypes of Gastric Cancer

T cell activation

OFF

T cell activation

OFF

Suppression of T cell activation by PD-1/PD-L1(or PD-L2) interaction3)

Escape from immune

surveillance3) Tumor cell

inactivated T cell

Attack against

tumor cells

OFF

Attack against

tumor cells

OFF

tumor cell inactivated T cell

PD-L2

PD-L1

PD-1

antigen-presenting cell(dendritic cells etc.)

1) Chen DS et al. Immunity 39: 1-10, 2013 　　　　

2) Mellman I et al. Nature 480: 480-489, 2011

3) Pardoll DM. Nat Rev Cancer 12: 252-264, 2012

antigen

presentation1,2)

naïve T cell

Lymph node

tumor-specific antigen

Migration and infiltration of T cells into tumors2)

Editorial supervision:

Division of Cellular Signaling Institute for Advanced Medical Research,

Keio University School of Medicine, Prof. Yutaka Kawakami

Escape from Immune Surveillance

T

cellsactiva

tion

OFF

T

cellsactiva

tion

OFF

Suppression of T cell activation

by PD-1/PD-L1(or PD-L2)

interaction 2,3)

Anti-PD-1 therapy

PD-L2PD-L1

tumor cell

PD-1

activated T cell

PD-L2

PD-L1

PD-1

Anti-PD-1 Therapy

Killing of tumor cells

by reactivation of T

cells5)

Tumor cell

inactivated T cell

Attack against

tumor cells

Attack against

tumor cells

antigen-presenting cell(dendritic cells etc.)

antigen

presentation 1,2)

naïve T cell

reactivation of T cells by suppression of PD-1/PD-L1(or PD-L2) interaction3,4)

Lymph node

tumor-specific antigen

Editorial supervision:

Division of Cellular Signaling Institute for Advanced Medical Research,

Keio University School of Medicine, Prof. Yutaka Kawakami

Cancel of Immunity Suppression

by Anti PD-1 Therapy

1) Chen DS et al. Immunity 39: 1-10, 2013; 2) Mellman I et al. Nature 480: 480-489, 2011

3) Pardoll DM. Nat Rev Cancer 12: 252-264, 2012; 4) Postow MA et al. J Clin Oncol 33: 1974-1982, 2015

5) Topalian SL et al. Curr Opin Immunol 24: 207-212, 2012

Line Study Agent Tested Targeting Control Arm Primary EP

1st ToGA (HER2) trastuzumab HER2 XP/FP OS

LOGiC(HER2) lapatinib HER2 XELOX OS

JACOB (HER2) pertuzumab HER2 XP + trastuzumab OS

AVAGAST bevacizumab VEGF XP OS

AVATAR bevacizumab VEGF XP OS

EXPAND cetuximab EGFR XP PFS

REAL-3 panitumumab EGFR EOX OS

RILOMET-1, 2 rilotumumab MET ECX, XP OS

METGastric onartuzumab MET mFOLFOX6 OS

RAINFALL ramucirumab VEGFR2 XP PFS (OS)

KEYNOTE 062 pembrolizumab PD-1 XP/FP PFS, OS

ATTRACTION-04 nivolumab PD-1 SOX/CapeOX PFS, OS

CheckMate-649 nivolumab,nivo+ipilimumab PD-1 FOLFOX/CapeOX OS in PD-L1+

GS-5745 (Gilead) andecaliximab MMP9 mFOLFOX6 OS

1st maintenance JAVELIN GASTRIC 100 avelumab PD-L1 FOLFOX/CapeOX PFS, OS

2nd TyTAN (HER2) lapatinib HER2 weekly paclitaxel OS

GATSBY (HER2) TDM-1 HER2 weekly paclitaxel OS

RAINBOW ramucirumab VEGFR2 weekly paclitaxel OS

REGARD everolimus mTOR BSC (Placebo) OS

ENRICH nimotuzumab EGFR irinotecan OS

GRANITE2 everolimus mTOR weekly paclitaxel PFS

GOLD olaparib PARP weekly paclitaxel OS

BRIGHTER BBI-608 STAT3 weekly paclitaxel OS

KEYNOTE 061 pembrolizumab PD-1 weekly paclitaxel PFS, OS in PD-L1+

2nd / 3rd GRANITE1 everolimus mTOR BSC (placebo) OS

3rd JAVELIN GASTRIC 300 avelumab PD-L1 Irinotecan/taxane OS

Apatinib Study (China only) apatinib VEGFR2 BSC (placebo) OS

3rd～ ANGEL apatinib VEGFR2 BSC (placebo) OS

ATTRACTION-02 nivolumab PD-1 BSC (placebo) OS

Global RCTs with

Molecular Targeting

Agents (Including PD-(L)1

Ab) for Metastatic GC

Treatment Pathways Currently under Evaluation

for Gastric Cancer

EGFR: epidermal growth factor receptor; STAT3: signal transducer and activator of transcription 3

Extensively Modified from Shah MA. J Clin Oncol 33:1760–1769, 2015

STAT3 ×STAT3 ×

Immune Checkpoint Inhibitor (Nivolumab ○)Immune Checkpoint Inhibitor (Nivolumab ○)

Angiogenesis (BEV ×, AFL×, RAM ○, <Apatinib ○>)Angiogenesis (BEV ×, AFL×, RAM ○, <Apatinib ○>)

EGFR ×EGFR ×

MET ??MET ??

>5,000 patients are planned to be enrolled in 19 ongoing studies,

with additional studies being planned

>5,000 patients are planned to be enrolled in 19 ongoing studies,

with additional studies being planned

FGFR ??FGFR ??

HER-2 (Tmab ○, T-DM1 ×, Lapatinib ×, Pertuzumab ×)HER-2 (Tmab ○, T-DM1 ×, Lapatinib ×, Pertuzumab ×)

Predicted ORR Across Tumor Types in 2L All-Comers

PFS Across Tumor Types in 2L All Comers

A Meta-Analysis to Indirectly Compare The Efficacy Profiles of Anti-PD-1/PD-L1

Monotherapy across Solid Tumors Using A Bayesian Hierarchical Model

Koneru M, et al. ASCO 2018

ORR PFS OS

Kang YK, et al. Lancet 2017

ORR PFS OS

Fuchs CS, et al. JAMA Oncol 2018

Patient,n

Events,n

mOS, months (95%CI)

12-month OS rate (95%CI)

Nivo.

330 2255.32(4.63, 6.41)

26.6(21.1, 32.4)

PLB.

163 1414.14(3.42, 4.86)

10.9(6.2, 17.0)

OS

0

0 2 4 6 8 10 12 14 16 18 20 22

Time, months

Pro

ba

bili

ty o

f su

rviv

al, %

100

80

60

40

20

HR 0.63 (95%CI 0.50, 0.78)

p<0.0001

Kang Y-K, et al. ASCO-GI, 2017

ORR: 11.2% (95% CI; 7.7-15.6)

ATTRACTION-02 (Nivolumab) KEYNOTE-059 (Pembrolizumab)

0

0

10

20

30

40

50

60

70

80

90

100

2 4 6 8 10 12

Overa

ll S

urv

ival, %

14 16 18 20 22Time, months

Median OS(95% CI), mos

12-month OS rate, %

All patients (n=259) 5.5 (4.2-6.5) 23.4

Fuchs CS, et al. ASCO, 2017

Wainberg ZA, et al. ESMO, 2017

OS

ORR: 11.6% (95% CI; 8.0-16.1)

Anti-PD-1 Antibody Monotherapy: Later Line for GC

N=330 N=259

N=163

Fuchs CS, et al. JAMA Oncology 2018

Q: Which is better, in earlier or later line

in case of using anti-PD-(L)1 antibody

for G/GEJ Cancer?

A: Probably earlier line is better

in terms of efficacy (ORR, OS).

Hui R. ASCO 2016

Brahmer JR, et al. WCLC 2017

KEYNOTE-001

KEYNOTE-024 Study Design

Reck M, et al. N Engl J Med 2016

Hui R, et al. ASCO 2016

Garon EB, et al. N Engl J Med 2015

OS ORR

Lessons from NSCLC

OS

KN-59 cohort 3N = 31

KN-59 cohort 1N = 259

ATTRACTION-02N = 330

Line 1L 3L or later 3L or later

PD-L1 + All comer + - All comer + -

ORR 26% 11.6% 16% 6% 11.2% - -

DCR 36% 27% 34% 19% 40.3%

mPFS 3.3m 2.0m 2.1m 2.0m 1.61m - -

mOS 20.7m 5.5m 5.8m 4.6m 5.3m 6.1m 5.2m

AE (Any) 77% 61% 43%

AE ( G3)≧ 23% 18% 11%

ORR And Waterfall in KEYNOTE-059 & Attraction-02

24 patients (77%) experienced

a reduction in target lesion size

Best Percentage Change in All Patients (n = 31)

–100

–80

–60

–40

–20

0

20

40

60

80

100

Ch

ange F

rom

Baselin

e, %

20% increase in tumor size

95 patients (42%) experienced

a reduction in target lesion size

Best Percentage Change in All Patients (n = 224)

Wainberg ZA, et al. ESMO, 2017 Fuchs CS, et al. JAMA Oncol 2018 Kang YK, et al. Lancet 2017

Phylogenetic Tree Analyses: Clonal And Subclonal Neoantigen

Heterogeneous tumors are composed of multiple subclones and under selection pressures, such as

chemotherapy, subclones with either intrinsic or acquired resistance can be selected for, allowing these

subclones to dominate a tumor mass and potentially drive disease progression.

Primary tumors consist of different subclones with shared and private somatic alterations. Alterations shared

by all tumor cells (A) occur early in tumorigenesis, represented by the blue trunk of the phylogenetic tree;

alterations shared by tumor cells present in some regions of the tumor but not all (B and C) occur later in

tumorigenesis, represented by the yellow branches of the tree; and private alterations (D–F) present in only

one region of the tumor also occur later in tumorigenesis, represented by the red branches of the tree.

Jamal-Hanjani M, et al. Clin Cancer Res 21:1258-1266, 2015

Clonal Neoantigens Elicit T cell Immunoreactivity

And Sensitivity to Immune Checkpoint Blockade

McGranahan N, et al. Science 351:1463-1469, 2016

A relationship between clonal neoantigen burden and overall

survival in primary lung adenocarcinoma was observed.

Sensitivity to PD-1 blockade in patients with advanced NSCLC

was enhanced in tumors enriched for clonal neoantigens.

T cells recognizing clonal neoantigens were detectable

in patients with durable clinical benefit.

Cytotoxic chemotherapy–induced subclonal

neoantigens, contributing to an increased mutational

load, were enriched in certain poor responders.

Q: What is a biomarker of anti-PD-(L)1

therapy in G/GEJ cancer?

A: 1) PD-L1 expression may be, but has not

been established robustly

2) MSI-H without doubt

3) TMB probably YES, but few data in GC

Shitara K, et al. Lancet 2018

KEYNOTE-061: Overall Survival, CPS 1%≧

Mok TS, et al. N Engl J Med 2009

IPASS: PFS, Gefitinib vs. CP

Is PD-L1 Expression Definite Biomarker in Anti-PD-1 Ab for GC?

Mok TS, et al. N Engl J Med 2009

IPASS (n=1218), PFS

KN-061, CPS 1% (n=395, 67%), ≧ OSCPS 10%≧

MSI-H

n=261 (21%)

n=108 (27%,18% )ITT population, n=592

n=27 (4.6% )

Shitara K, et al. Lancet 2018

0 2 4 6 8 10 12 14 16 18 20 22 24 26 28

0

10

20

30

40

50

60

70

80

90

100

Pro

bab

ility

of

Su

rviv

al (

%)

Overall Survival by PD-L1 Expression <1% vs ≥1%

0 2 4 6 8 10 12 14 16 18 20 22 24 26 28

0

10

20

30

40

50

60

70

80

90

100

PD-L1 <1% PD-L1 ≥1%

Hazard ratio, 0.58

(95% CI, 0.24–1.38)

Median OS, months (95% CI)

Nivolumab (n=16) 5.2 (2.8–9.4)

Placebo (n=10) 3.8 (0.8–5.0)

Ove

rall

Su

rviv

al

(%)

114100

75 56 49 42 37 24 15 11 7 4 3 1 0

52 40 27 22 16 14 11 6 5 4 3 2 2 2 0

16 15 10 7 5 4 4 2 2 0 0 0 0 0 0

10 8 4 2 1 1 1 0 0 0 0 0 0 0 0

Nivolumab

Placebo

Months MonthsNo. at Risk

Median OS, months (95% CI)

Nivolumab (n=114) 6.1 (4.8–8.6)

Placebo (n=52) 4.2 (3.0–6.9)

Hazard ratio, 0.71

(95% CI, 0.50–1.01)

Boku N, et al. ESMO 2017

Evaluable for PD-L1 expression, n (%)≥1% vs <1%≥5% vs <5%

Nivo: 130 (39)16 (12) vs 114 (88)10 (8) vs 120 (92)

Placebo: 62 (38)10 (16) vs 52 (84)7 (11) vs 55 (89)

Among PD-L1–evaluable patients, baseline characteristics between nivolumab and placebo arms were similar

ATTRACTION-02: Nivolumab

Hellmann MD, et al. N Engl J Med. 2018

Low TMB 1Y-PFS MST 95%CI

Nivo ＋ Ipi 26% 3.2 M 2.7-4.3

Chemotherapy 17% 5.5 M 4.3-5.6

HR 1.07 (95%C.I. 0.84-1.35)High TMB: defined as 10MT/Mb by Foundation One

HR 0.58 (95%C.I. 0.41-0.81)

p<0.001

High TMB 1Y-PFS MST 95%CI

Nivo ＋ Ipi 42.6% 7.2 M 5.5-13.2

CTx 13.2% 5.5 M 4.4-5.8

No. at risk

IPI+NIVO

CTx

PFS

NSCLC

CTx naïve

No genetic alteration

PD-L1 1%≧

N=1189

PD-L1 ＋ 1%

N=550

IPI+NIVO

(N=139)

CTx

(N=160)

Lessons from NSCLC (TMB)

CheckMate-227

Janjigian YY, et al. Cancer Discovery, 2018

MSI-H TMB

Megan G, et al. #4056, ASCO 2018

TMB for G/GEJ Cancer, ASCO 2018MSK-IMPACTTM (468-gene platform)

Cut off 7.3 MT/megabases

N=120 (MSI-H, N=7)

‘SCRUM JAPAN’ by OCP panel (143-gene platform)

Panel is possible instead of WES,

but optimal ‘cut off’ is not established

Panel is possible instead of WES,

but optimal ‘cut off’ is not established

cf: 5.0 in Foundation One Panel

Nakamura Y, et al. #12094, ASCO 2018

Q: Are there any substantial rationales

regarding IO-combo therapy?

A: 1) IO + cytotoxic agents (chemotherapy)

2) IO + IO

3) IO + anti-angiogenic inhibitor (including

other molecular targeting agents)

4) IO + radiotherapy

Combined with Chemotherapy

- Is It Good or Evil?

Gandhi L, et al. AACR 2018

Emens LA, et al. Cancer Immunol Res 2015

Cytotoxic Agents Enhances Immunological Reaction

around Tumor and Tumor Microenvironment

Tumor cells can upregulate

expression of immune target

molecules such as Fas and

MHCI following irradiation.

Irradiation can also

normalize dilated and chaotic

blood vessels to enable T

cells to access tumors.

The Effects of Chemotherapy And Radiotherapy

on The Tumor Microenvironment

Kershaw MH, et al. OncoImmunology, 2013

Ox can also lead to an increased proportion of proinflammatory, M1,

macrophages relative to alternatively activated, M2, macrophages.

Anthracyclines can recruit APCs and enhance their differentiation to

an activated phenotype, better able to present antigen to lymphocytes.

Ox can induce immunogenic cell

death, which can lead to the release

of tumor antigens for uptake and

processing by antigen presenting

cells (APC).

Gem, Ox and Pacli

can reduce the

frequency of

MDSC and/or Treg

infiltrating tumors,

thereby reducing

their immuno-

suppressive

effects.

Increases in

intratumoral T cells

can also be achieved

using antibodies

against VEGF.

Attraction-04 Part 1 Efficacy

Kang YK et al. ESMO, 2017

KN 059-Cohort 2: Best Percentage Change and

Longitudinal Change in Target Lesion Size

aOnly patients with measurable disease per RECIST v1.1 by central review at baseline who had ≥1 postbaseline assessment were included (n = 25); assessment was nonevaluable for 1 patient.bLongitudinal change in the sum of the longest target lesion diameters from baseline in patients with ≥1 postbaseline assessment (n = 25).+No progressive disease at last disease assessment.

24 patients (96%) experienced a reduction in target lesion size

–100

–80

–60

–40

–20

0

20

Ch

an

ge

Fro

m B

as

eli

ne

, %

PD-L1 positive

PD-L1 expression unknown

PD-L1 negative Ch

an

ge

Fro

m B

as

eli

ne

, %

Best Percentage Change in All Patients (n=25)a

Cohort 2

No prior therapy

PD-L1 positive or

negative

Cohort 2

No prior therapy

PD-L1 positive or

negative

Pembrolizumab 200 mg Q3W +

Cisplatin 80 mg/m2 Q3W +

5-FU 800 mg/m2 Q3W or

Capecitabine 1000 mg/m2 BID Q3Wa

Pembrolizumab 200 mg Q3W +

Cisplatin 80 mg/m2 Q3W +

5-FU 800 mg/m2 Q3W or

Capecitabine 1000 mg/m2 BID Q3Wa

aCapecitabine was administered only in Japan

Study Design

Wainberg ZA, et al. ESMO, 2017

ORR:

17/25 (68%)

mOS:

13.8 mo

Janjigian YY, et al. ASCO 2017

Primary endpoint:

• ORR per RECIST v1.1

Secondary endpoints:

• OS, PFS, TTR, DOR• Safety

Exploratory endpoint:

• PD-L1 tumor expression (Dako 28-8 pharmDx assay)

Primary endpoint:

• ORR per RECIST v1.1

Secondary endpoints:

• OS, PFS, TTR, DOR• Safety

Exploratory endpoint:

• PD-L1 tumor expression (Dako 28-8 pharmDx assay)

Checkmate 032 EG Cohort

DOR, duration of response; EG, esophagogastric (including gastric/esophageal/gastroesophageal junction

cancer); TTR, time to response.

* Nivolumab + ipilimumab administered for 4 cycles followed by nivolumab 3 mg/kg IV Q2W. † Time from first dose to data cut-off; follow-up was shorter for patients who died prior to data cut-off.

Nivolumab 3 mg/kg +

Ipilimumab 1 mg/kg IV

Q3W*

(NIVO 3 + IPI 1)

Nivolumab 3 mg/kg +


Q3W*

(NIVO 3 + IPI 1)

Nivolumab 1 mg/kg +


Q3W*

(NIVO 1 + IPI 3)

Nivolumab 1 mg/kg +


Q3W*

(NIVO 1 + IPI 3)

Nivolumab 3 mg/kg IV Q2W

(NIVO 3)

Nivolumab 3 mg/kg IV Q2W

(NIVO 3)

Western patients with advanced/metastatic EG cancer

with progression on ≥1 prior chemotherapy

N = 160

Western patients with advanced/metastatic EG cancer

with progression on ≥1 prior chemotherapy

N = 160

Median (range)

follow-up, mo†:28 (17 to 35) 24 (21 to 33) 22 (19 to 25)

* Investigator review.

# Patients with confirmed response (complete or partial response).† Patients with 0% best reduction in target lesion, including 3 patients with PD-L1 ≥1%

(NIVO 3, n=2; NIVO 3 + IPI 1, n=1) and 1 patient with PD-L1 <1% (NIVO 1 + IPI 3).change truncated to 100%

†

##

#

#

#

#

# #

## #

100

75

50

25

0

-25

-50

-75

-100

Be

st

Red

uc

tio

n f

rom

Bas

eli

ne i

n T

arg

et

Le

sio

ns

* (%

)

#

#

##

#

100

75

50

25

0

-25

-50

-75

-100

Be

st

Red

uc

tio

n f

rom

Ba

seli

ne i

n T

arg

et

Les

ion

s*

(%)

†

PD-L1 < 1% PD-L1 ≥ 1% PD-L1 not evaluable/missing

100

75

50

25

0

-25

-50

-75

-100

Be

st

Red

ucti

on

fro

m B

as

eli

ne i

n T

arg

et

Le

sio

ns

* (%

)

#

#

#

#

#

#

#

† †

Best Reduction in Target Lesions

Responses were observed regardless of PD-L1 expression

ORR: 12%

Janjigian YY, et al. ASCO 2017

ORR: 24% ORR: 8%

NIVO 1 + IPI 3PD-L1–evaluable patients, 38 of 42


NIVO 3PD-L1–evaluable patients, 38 of 53

NIVO 3PD-L1–evaluable patients, 38 of 53



KEYNOTE-062 (1L)Checkmate-649 (1L)

Attraction-04 (1L)

Ongoing 1L-Combination Trials

Any PD-L1

1st-line

N=1266 　Primary Endpoint: OS (PD-L1+)

PD-L1+

1st-line

N=750 　

Primary Endpoint: PFS, OS

Primary Endpoints: PFS, OS

Any PD-L1

1st-line

N=650 　

JVDF/KN-098 Phase 1a/b Study DesignRAM + Pembro

J. Exp. Med. 2015 Vol. 212 No. 2 139–148

Herbst RS, et al. ASCO 2018

Phase 1 StudyRAM + Durvalumab

Golan T, et al. WCGC 2017

Nivo + Ram as IIT-PII

Takahari D et al. ASCO 2018

PTX + Ram + Nivo as IIT-PII

Nishina T, et al. ASCO 2018

Loi S, et al. SABCS 2017

Catenacci D VT, et al. ASCO 2018

G/GEJC (Pembro+margetuximab)

BC (Pembro+trastuzumab)

Stagg J et al. PNAS 108 : 7142-7147, 2011

Anti-HER2 Therapy for BC, G/GEJC

Pretreated Trastuzumab

IO Combinations: Others

Anti-PD-(L)1 Inhibitor +

Bevacizumab: NSCLC, HCC..

Lenbatinib: H&N, HCC, RCC, EC..

Axitinib: RCC..

BBI-608: CRC..

IDO Inhibitor: TNBC, Melanoma↓..

LAG-3 Inhibitor: multi-type of cancer..

CCR-4 Inhibitor: HCC, PC, NSCLC, SCLC,

E/G/GEJC..

M7824 (TGF-β+(avelumab)): E/G/GEJC…

Ngwa W, et al. Nat Rev Cancer 18:313-322, 2018 Sato H, et al. Nature Commun 24::1751, 2017

Durvalumab (Lung ： PACIFIC trial) Nivo+SBRT (H&N)

Mcbride SM, et al. ASCO 2018Antonia SJ, et al. N Engl J Med 377: 1919-1929, 2017

TAA

Abscopal Effect RT upregulates PD-L1

IO + RT

PembrolizumabPTX

Niv olumabplacebo

pembrolizumab

pembrolizumab+XP/FP

pembrolizumab

Ipilimumabplacebo

Olaparib+PTXOlaparib

Ev erolimusPlacebo

ECX+rilotumumabECX

FOLFOX+onartuzumabFOLFOX

Irinotecan+nimotuzumabIrinotecan

EOC+panitumumabEOC

XP+cetuximabXP

ApatinibPlacebo

PTX+RamcirumabPTX

RamucirumabPlacebo

Ramcirumab+XP/FPXP/FP

XP+Bev acizumabXP+placebo

T-DM-1PTX or DTX

PTX + LapatinibPTX

CapeOX + lapatinibCapeOX

FP/XP+trastuzumabFP/XP

FP/XP+trastuzumab+perutsuzumabFP/XP+trastuzumab

0 5 10 15 20 25

target Study Line ph OS Treatment

HER2

JACOB 1 3 ×

ToGA 1 3 ＋

Logic 1 3 ×

TyTAN 2 3 ×

GATSBY 2 3 ×

VEGF/VEGFR

AVAGAST 1 3 ×

RAINFALL 1 3 ×

REGARD 2 3 ＋

RAINBOW 2 3 ＋

Apatinib 3 3 ＋

EGFR

EXPAND 1 3 ×

REAL-3 1 3 ×

ENRICH 2 3 -

HGF RILOMET1 1 3 ×

MET METGastric 1 3 ×

mTOR GRANITE-1 2/3 3 ×

PARP GOLD 2 3 ×

CTLA-4 maintenance 1 2 ×

PD-1

KN59 ch3 1 2 -

KN59 ch2 1 2 -

KN59 ch1 3 ＋ 2 -

ATTRACTION-02 3 ＋ 3 ＋

KN61 2 3 ×

Extensively Modified from Shitara K, Gastric Cancer 2017

OS Data from Global Trials against GC/GEJC

Summary

• Anti-PD-1 antibody monotherapy (Pembrolizumab and Nivolumab)

are both active and having similar efficacy in late line of G/GEJC,

but the efficacy (such as long survival) is limited to few populations.

• Anti-PD-1 antibody combined with other agents (cytotoxic,

molecular targeting agent such as anti-angiogenic, and other

immuno-oncological agent) demonstrates encouraging efficacy and

may promise the position of earlier line therapy for G/GEJC.

• The role of PD-L1 expression and relationship between PD-L1

expression and efficacy are needed to be further investigated in

G/GEJC.

• Many clinical trials in any line or any combinations are now

ongoing, and these results will be confirmed as definite therapy for

G/GEJC.

Acknowledgment

Thank you

disclosure - oncology leanring network · presentation 1,2) naïve t cell reactivation of t cells...

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