Chaitali Nangia,1 Mira Kistler,1 Lennie Sender, 1 John H. Lee,2 Frank Jones,3 Patrick Soon-Shiong2

NANT Cancer Vaccine (NCV): An Orchestration of Immunogenic Cell Death by Overcoming Immune Suppression and Activating Natural Killer (NK) and T Cell

Therapy in Patients with Greater Than 3rd-Line Triple-Negative Breast Cancer (TNBC) or Head and Neck Squamous Cell Carcinoma (HNSCC)

1Chan Soon-Shiong Institute for Medicine, El Segundo, CA, USA; 2NantKwest, Inc, Culver City, CA, USA; 3NantCell, Inc, Culver City, CA, USA

Study Design• Non-randomized, open-label, Phase 1b/2 trials.• Combination low dose metronomic chemotherapy,

immunotherapy and CD16 haNK administered over a 3-week induction cycle for up to 1 year.

Enrollment Criteria• Histologically confirmed or unresectable TNBC

Methods

ResultsSafety• Four patients with HNSCC received 44 doses of CD16 haNK with NCV.• Seven patients with TNBC received 54 doses of CD16 haNK with NCV.• No patient experienced cytokine release syndrome or immune related adverse events from CD16 haNKs

or the immune components of NCV.• Three HNSCC patients experienced chemotherapy related DLTs.• No TNBC patients experienced chemotherapy related DLTs.

Conclusions• The Nant Cancer Vaccine (NCV) treatment regimen was tolerated in all patients who received haNK with no

evidence of cytokine release syndrome or immune related adverse events after a total 98 infusions. • These findings suggest that haNK cell therapy given in combination with low-dose chemotherapy, localized

radiation, and immune modulators may be safely used in treatment of patients with advanced TNBC and HNSCC.

• In heavily pretreated patients with advanced cancer, the NCV treatment regiment has yielded preliminary positive clinical results with 80% disease control in patients with TNBC with advanced disease ranging from 4th to 6th line therapy.

• Furthermore, in patients with advanced Head & Neck cancer ranging from 4th to 6th line therapydemonstrated 67% disease control, with a pathologically confirmed complete response in one patient.

References and Acknowledgements

© 2018 NantKwest, Inc. All Rights Reserved.

TNBCQUILT-3.067

HNSCCQUILT-3.090

Mean age (min, max)

49.4 (36, 57)

63.5 (50, 76)

Gender 7 female 4 male

ECOG status 0 (6 patients)1 (1 patient)

0 (1 patient)1 (3 patients)

Diagnosis to study entry (years)

2.7(1.2, 4.5)

1.7(1.0, 3.3)

Line of therapywith NCV 4.6 ± 1.0 5.0 ± 0.8

TNBCNumber of Patients (% Incidence)

HNSCCNumber of Patients (% Incidence)

All AEs Grade ≥ 3 SAEs All AEs Grade ≥ 3 SAEs

Any AE 6 (100%) 5 (83%) 2 (33%) 4 (100%) 4 (100%) 2 (50%)

Anemia 2 (33%) 1 (17%) 0 4 (100%) 3 (75%) 0

Fatigue 6 (100%) 1 (17%) 0 4 (100%) 1 (25%) 0

Febrile neutropenia 1 (17%) 1 (17%) 0 2 (50%) 2 (50%) 1 (25%)

Neutropenia 2 (33%) 2 (33%) 0 1 (25%) 1 (25%) 0

Pyrexia 4 (67%) 2 (33%) 0 4 (100%) 0 1 (25%)

Table 2: Chemotherapy Related AE Incidence by Patient

Endpoints• Primary endpoints: Incidence of treatment-emergent adverse events (AEs) and serious AEs (SAEs).• Secondary endpoints: overall response rate (ORR), progression-free survival (PFS), overall survival (OS),

duration of response (DOR), disease control rate (DCR), and quality of life by patient-reported outcomes (PROs).

Figure 2: Timeline of Treatment with NCV Therapy Figure 3: Best Target Lesion Response

Table 1: Patient Demographics and Cancer History

that has progressed on or after anthracycline-based chemotherapy; or HNSCC with progression on or after platinum-based chemotherapy and anti-PD-1/PD-L1 therapy.

• ≥ 18 years old with ECOG performance status of 0–2.

Figure 1: Resolution of an HNSCC Parotid Tumor

NCV treatment initiated

May 2018

May 4, 2018: Baseline imaging assessment. Ulcerated right parotid mass.

June 22, 2018: Complete resolution of parotid tumor, with no evidence of disease.

As of October 2018, 7 of 11 enrolled patients continue to be treated with NCV therapy. 3 of 8 evaluable patients experienced irPRs.‡Magnitude of PD unavailable.*Continue to receive NCV therapy on study.

SITC 2018. November 7-11, 2018, Washington, DC, USA

1) Siegel RL et al. CA Cancer J Clin. 2018;68:7-30. 2) NCCN: Head and Neck Cancers (Version 2.2018). 3) Rakha EA et al. J Clin Oncol. 2008;26:2568-81. 4) Mandal M et al. Cancer. 2008;112:2088-2100.5) Schettini F et al. Cancer Treat Rev. 2016;50:129-141. 6) Desai N et al. Transl Oncol. 2009;2:59-64. 7) Smith BD et al. J Clin Oncol. 2000;18:2046-52. 8) Linderholm BK et al. Ann Oncol. 2009;20:1639-46. 9) Zhang L et al. Clin Immunol 2008; 129:219-29. 10) Seidel UJ et al. Immunol 2013; 4:76. 11) Kim PS Oncotarget 2106; 7:16130-45. 12) Melief CJ, et al. J Clin Invest 2015; 194:1013-20. This study is sponsored by NantKwest, Inc. We thank Eric Carlson, MS, Barry Simon, MD, and Hui Zhang, MS, for analyses and critical input. Medical writing support was provided by Sharif Taha, PhD.

NANT Cancer Vaccine (NCV)• The NCV includes metronomic low-dose nab-paclitaxel (Abraxane) and low dose radiation therapy with

cryopreserved off-the-shelf CD16 targeted natural killer cells (haNK) and cytokine NK & T cell superagonist IL-15RαSu/Fc (N-803) combined with E2b-deleted adenovirus (Ad) & yeast (Ye) tumor associated antigen vaccines, and checkpoint inhibitors.

• All treatment was administered in the outpatient setting without G-CSF support.• The NCV is anticipated to reduce immunosuppression in the tumor microenvironment, while increasing

immune-mediated cell death, cytotoxic dendritic and T cell activity, and innate immune responses. 9-12

• Ongoing phase 1b/2 studies for TNBC (QUILT-3.067; NCT03387085) and HNSCC (QUILT-3.090; NCT03387111) seek to evaluate the safety of the NCV and establish preliminary estimates of efficacy.

• As of October 2018, 98 doses of haNK and NCV Vaccine has been administered in 11 patients(7 TNBC, 4 HNSCC, See Table 1)

5443353335

3

M 51 6

M 76 5

M 61 5

M 67 4

F 57 4

F 36 6

F 53 4

F 49 4

F 50 4

F 56 6

F 46 4

Line of therapy with NCVSex Age

TNBC and HNSCC• Advanced TNBC and HNSCC are aggressive cancers with limited treatment options.1-2• TNBC and HNSCC share cytological and molecular features, including originating in epithelial or

epithelial-like cells, responsivity to treatment with nab-paclitaxel, and VEGF expression as a poor prognostic factor. 3-8

Background Efficacy• Head & Neck: DCR is 67% for 2 of 3 evaluable patients who experienced SD for ≥ 8 weeks.

1 patient with 5th line HNSCC experienced a pathologically confirmed complete response. This patient showed resolution of an ulcerated right parotid mass (-100% change in tumor size from baseline; Figure 1). Progression was recorded on a subsequent assessment, resulting in a confirmed irPR.

• TNBC: DCR is 80% in 4 of 5 patients with SD in 2 patients and irPR in 2 patients, with treatment still ongoing.

• For all patients, Figure 2 shows the timeline of NCV treatment for all enrolled patients (11 total). Figure 3shows the best target lesion response for patients with ≥ 1 evaluable imaging assessment (8 patients).

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