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 Metastatic Pancreatic Cancer

MethodsStudy Design ( QUILT-3.070)• Non-randomized, open-label, single-arm phase 1b/2 trial.• Combination chemotherapy, CD16 haNK, and

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

Enrollment Criteria• Histologically-confirmed metastatic pancreatic

adenocarcinoma that has progressed after SoC therapy.• ≥ 18 years old with ECOG performance status of 0–2.

AcknowledgmentsThis study is sponsored by NantKwest, Inc. The authors thank Eric Carlson, MS, and Hui Zhang, MS, for data analysis and critical input. Medical writing support was provided by Sharif Taha, PhD.

ResultsSafety• No DLTs have occurred on study to date.• Patients received 15.2 � 7.0 (mean�SD) doses of haNK

per patient, with a total of 152 doses administered with no evidence of cytokine release syndrome (CRS).

• In the NCV treatment regimen, haNK cell therapy was administered concurrently with the PD-L1 IgG1 antibody avelumab. No immune-related treatment-emergent, haNK-related AEs occurred.

• The most common treatment-emergent, treatment-related grade ≥ 3 AEs were neutropenia (8 of 10 patients) and anemia (6 of 10 patients), consistent with AEs associated with chemotherapy, are summarized in Table 2.

NANT Cancer Vaccine (NCV) to Induce Immunogenic Cell Death• 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 NK and T cell activity, and innate immune responses.3-6

• The ongoing phase 1b/2 study (QUILT-3.070; NCT03387098) seeks to evaluate the overall safety profile of the NCV and to establish preliminary estimates of efficacy. The previously opened, closely-related studies QUILT-3.039 and QUILT-3.060 used similar treatment regimens.

• As of October 2018, 171 doses of haNK and NCV Vaccine has been administered in 10 patients (Table 1) have been enrolled.

Conclusions• The NCV treatment regimen was well tolerated in 10 patients with greater than third line metastatic pancreatic cancer,

suggesting that haNK cell therapy given in combination with low-dose chemotherapy, localized radiation, and immune modulators can safely be used to treat patients with advanced cancer.

• Administration of multiple cycles of haNK therapy in combination with a PD-L1 inhibitor did not elicit haNK-related immune AEs, suggesting these therapies may be safely tolerated while promoting patient anticancer immune responses.

• In a highly treatment-refractory patient population, the NCV treatment regimen resulted in a DCR of 90% (SD for ≥ 8 weeks), and a median PFS and OS of 5.8 months and 9.5 months, respectively, suggesting that the NCV shows promise in treating advanced metastatic pancreatic cancer previously targeted with multiple lines of therapy.

• The median overall survival of 9.5 months in these patients with greater than 3rd line disease compares favorably with historical median overall survival in 1st line pancreatic cancer patients receiving gemcitabine + Abraxane of 8.7 months7

References1) National Cancer Institute. www.cancer.gov. 2) Pelzer U, et al. Eur J Cancer 2011;47:1676-81. 3) Zhang L et al.Clin Immunol 2008; 129:219-29. 4) Seidel UJ et al. Immunol 2013; 4:76. 5) Kim PS Oncotarget 2106; 7:16130-45.6) Melief CJ, et al. J Clin Invest 2015; 194:1013-20. 7) Goldstein D, et al. JNCI Natl Cancer Inst 2015;107:dju413

© 2018 NantKwest, Inc. All Rights Reserved. SITC 2018. November 7-11, 2018, Washington, DC, USA

Patient Demographics and Cancer HistoryMean age (min, max) 53.5 (35, 66)

Gender 6 male4 female

ECOG status 0 (8 patients)1 (2 patients)

Diagnosis to study entry (years) 1.2(0.2, 2.2)

Line of therapy with NCV 3.7 ± 0.8

Endpoints• Primary endpoint: 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 (QoL) by patient-reported outcomes (PROs).

Fig. 2: Patient Treatment Course Fig. 3: Best Target Lesion Response

Table 1

Number of Patients (% Incidence)

All AEs Grade ≥ 3 AEs SAEs

Any AE 10 (100%) 9 (90%) 4 (40%)Anemia 6 (60%) 6 (60%) 0Diarrhea 9 (90%) 0 0

Fatigue 9 (90%) 0 0

Febrile neutropenia 2 (20%) 2 (20%) 1 (10%)

Infusion site reaction 10 (100%) 0 1 (10%)

Neutropenia 9 (90%) 8 (80%) 0Peripheralneuropathy 8 (80%) 0 0

Pyrexia 7 (70%) 2 (20%) 0

Efficacy• As of October 2018, the Disease Control Rate (DCR) for the study was 90%, with 9 of 10 patients

exhibiting stable disease (SD) for ≥ 8 weeks.• Median PFS was 5.8 months (95% confidence interval [CI]: 3.3, 8.8) and Median OS was 9.5 months

(95% CI: 5.0, upper limit not yet reached).

M 35 3

F 59 5

M 52 3

F 59 4

F 50 3

M 56 3

M 63 5

F 66 3

M 56 4

M 40 4

Sex Age

Tara Seery,1 Arvind Shinde,1 Mira Kistler,1 Lennie Sender,1 Anand Annamalai,1 Omid Jafari4 Frank Jones,2 John H. Lee,3 Patrick Soon-Shiong,3

Efficacy (continued)• 1 patient demonstrated resolution of a metastatic lung tumor within 8 weeks of initiating the NCV therapy

(Figure 1). The best overall response for this patient was a 28% reduction in tumor burden.• The timeline of NCV treatment is summarized in Figure 2 for each patient, and the best target lesion

response for each patient is shown in Figure 3.

BackgroundPancreatic Cancer• Pancreatic cancer is an aggressive and lethal disease. Annually, > 50,000 patients in the US are diagnosed

and > 40,000 die from the disease.1• There is a strong unmet need for novel pancreatic cancer treatments. Patients treated with greater than third-

line standard-of-care (SoC) chemotherapy have poor prognoses with a median OS of less than 2-4 months.2

Table 2: AE Incidence by Patient

1Chan Soon-Shiong Institute for Medicine, El Segundo, CA, USA; 2NantCell, Inc, Culver City, CA, USA; 3NantKwest, Inc, Culver City, CA, USA; 4Medical Imaging Center of Southern California, Santa Monica, CA, USA

Line of therapy with NCV

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Fig. 1: Resolution of a Metastatic Lung Tumor in a Patient with Pancreatic Cancer Refractory to Chemotherapy and Radiation Therapy

NCV Treatment

January 31, 2018: Baseline imaging assessment. Metastatic lung tumor

April 19, 2018: Resolution of lung tumor after 8 weeks of treatment.

NCV Treatment

On Treatment

Withdrawn

PD

Off Treatment

Death