NantKwest announced plans for a Phase 2, randomized, open-label study to evaluate the efficacy and safety of their combination immunotherapy: NantKwest’s PD-L1 t-haNK, ImmunityBio’s N-803, and aldoxorubicin HCI plus standard of care, versus standard-of-care chemotherapy for first- and second-line treatment of locally advanced or metastatic pancreatic cancer.

Four metastatic pancreatic cancer patients have been treated with PD-L1 t-haNK and N-803 under single patient INDs, with two patients on treatment for an evaluable period. One patient reported ongoing, durable, complete response six months after treatment, and one observed response of stable disease. The Investigational New Drug (IND) application has received authorization from the U.S. Food and Drug Administration (FDA) with the study anticipated to begin in June 2020.

“Our results from expanded access use of PD-L1 t-haNK in combination with N-803 offer proof-of-concept that, together with these agents, the immune system may play a role to activate robust and durable responses in metastatic cancer patients who have failed all standard-of-care therapies,” said Patrick Soon-Shiong, M.D., Chairman and Chief Executive Officer of NantKwest and ImmunityBio. “Based on these encouraging data, we are moving forward with a randomized Phase 2 program that will evaluate our immunotherapy combination on top of standard of care, compared to standard of care alone, in first- and second-line treatment settings. This unique approach to orchestrating the innate and adaptive immune systems to induce immunogenic cell death may be an important new approach for pancreatic cancer patients—these being among the most challenging to treat with poor prognoses.”

“Abraxane, a protein-based nanoparticle that activates macrophages, was our first evolution in making an impact on pancreatic cancer. With this addition of PD-L1 t-haNK and N-803, we are hopeful that we can proceed to the next step of long-term remission in this difficult to treat disease. Adding a natural killer cell with a checkpoint via PD-L1 t-haNK and activating memory T cells via N-803 will complete the ‘triangle offense’ we are orchestrating. The early results of complete response in one patient using the therapy on a compassionate use basis is encouraging and we are excited to initiate this trial involving other patients who suffer from pancreatic cancer,” he said.

Study Details:

This Phase 2, randomized, two-cohort, open-label study will evaluate the comparative efficacy and overall safety of standard-of-care chemotherapy versus standard-of-care chemotherapy in combination with PD-L1 t-haNK, N-803, and aldoxorubicin HCl in subjects with locally advanced or metastatic pancreatic cancer (QUILT-88). Each treatment setting, and first- and second-line or later maintenance, will be evaluated independently as Cohort A and Cohort B, respectively, with each Cohort having independent experimental and control arms. The study will initially enroll 268 subjects across both cohorts with the primary objective of comparative efficacy by progression free survival (PFS) per RECIST V1.1. Secondary objectives include initial safety and additional efficacy measures, including overall response rate (ORR), complete response (CR) rate, durability of response (DoR), disease control rate (DCR), and overall survival (OS).

Pancreatic cancer kills an estimated 47,000 people annually; it is the fourth leading cause of cancer-related death in the U.S., and 57,600 new cases are expected in 2020. Less than 5% of these patients will live for more than five years after diagnosis, and the median survival prognosis is 5 to 8 months.