PD-L1/CD16 Bispecific NK Cell Therapy PD-L1 t-haNK Doubles Overall Survival in Metastatic Pancreatic Cancer

January 18, 2021 News /Bio ValleyBIOON/ --NantKwest is a pioneering immunotherapy company focused on harnessing natural killer (NK) cells to treat cancer, infectious diseases, inflammatory conditions, and disorders of the innate immune system. Recently, the company jointly announced early interim results from the PD-L1 t-haNK trial with another immunotherapy company, ImmunityBio. The data showed that in the absence of otherFDAAmong patients with advanced metastatic pancreatic cancer approved for the treatment regimen, the median survival rate with the PD-L1 t-haNK combination therapy was twice that of the historical survival rate. These trials were based on the initial Cancer Moonshot hypothesis and the exploratory QUILT trial launched in 2017, and the results appear to validate a theory:By coordinating NK cell and T cell therapies, survival rates can be improved without high-dose chemotherapy.

Early collaborative Cancer Moonshot trials involve the combination of cell therapies and immunotherapies from multiple biotechnology and pharmaceutical companies, including NantKwest, ImmunityBio, Celgene, andPfizer. These trials explored the hypothesis that a paradigm shift in cancer treatment, achieved by activating the patient’s own immune system, could evolve into a modality capable of eradicating cancer cells without the need for high-dose chemotherapy.

From 2017 to 2020, multiple QUILT clinical trials exploring the combined application of these cell therapies, immunomodulatory antibodies, adenovirus-based cancer vaccines, and low-dose chemotherapy provided preliminary results, showing: in the absence of otherFDAIn patients with metastatic pancreatic cancer receiving the approved treatment regimen, median survival can more than double, and complete remission can be achieved. Based on data from these trials, ImmunityBio is conducting a pivotal three-cohort study in metastatic pancreatic cancer.Clinical Trial（QUILT88）。

PD-L1 t-haNK cells are a human-derived allogeneic NK cell line, engineered to express a chimeric antigen receptor (CAR) targeting PD-L1, originating from NantKwest’s proprietary NK-92 (aNK) master cell bank. In addition to targeting PD-L1, PD-L1 t-haNK cells are also engineered to express a high-affinity variant of the CD16 receptor (V158 FcγRIIIa), which mediates antibody-dependent cellular cytotoxicity (ADCC) by binding to monoclonal antibodies previously attached to cancer cells, thereby promoting the elimination of cancer cells. This means that the therapy can be applied in combination with other targeted approaches.

On December 21, 2020, ImmunityBio and NantKwest entered into a merger agreement, with the merger expected to be completed in the first half of 2021, creating a company focused onTumorA leading immuno- and cell therapy company in oncology and infectious diseases.

The interim study results announced are as follows:

In the Cancer Moonshot QUILT trial completed in 2019, which evaluated haNK cells in combination with the PD-L1 inhibitor avelumab, the median overall survival (OS) more than doubled among the 12 treated patients (median OS: 8 months vs. 3 months [historical control group]).When PD-L1 t-haNK was used to replace haNK and the PD-L1 inhibitor avelumab, one patient achieved complete remission. Of the five patients, four remained alive 8–16 months after initiating these expanded regimens, and the median overall survival (OS) had not yet been reached.

A single-arm Phase 2 trial (QUILT 88, Cohort C) was initiated in October 2020, with overall survival (OS) as the primary endpoint. Among the 18 patients with second-line or later-line pancreatic cancer enrolled, 15 (83%) remain alive to date. The Phase 2 randomized trials for first-line and second-line metastatic pancreatic cancer (QUILT 88, Cohorts A and B) are currently actively enrolling patients at three clinical sites.

Dr. Patrick Soon-Shiong, Chairman and Chief Executive Officer of ImmunityBio, stated, “The goal of the Cancer Moonshot initiative is to explore the hypothesis that coordinating natural killer cells and T cells could bring about a paradigm shift in cancer treatment. Preliminary results from these Cancer Moonshot trials, which combine immunotherapeutic agents—including Celgene’s Abraxane, NantKwest’s haNK, ImmunityBio’s Anktiva, and Pfizer’s PD-L1 inhibitor avelumab—have provided promising early data suggesting that multipleTumormedian overall survival in patients with advanced metastatic disease of this type could potentially double.”

Dr. Patrick Soon-Shiong also stated, “For five patients who had no other treatment options, we replaced haNK and avelumab with the NK cell therapy PD-L1 t-haNK, and we were pleased to observe a complete response in the first patient receiving this combination therapy. To date, four out of these five patients remain alive after initiating treatment. These observations confirm our hypothesis that activating patients through low-dose chemo-immunomodulatory therapyAutoimmunity"The system can improve prognosis. Based on our preliminary study, we initiated the QUILT 99 randomized trial for metastatic pancreatic cancer, and today we are pleased to present these findings, including survival data from Cohort C. Although this data is still early, the doubling of overall survival is encouraging and warrants further confirmation through research." (Bioon.com)

Original Source: NantKwest, ImmunityBio Announce Positive Interim Data on Survival Rates in Metastatic Pancreatic Cancer Trials