NANT cancer vaccine an orchestration of immunogenic cell death by overcoming immune suppression and activating NK and T cell therapy in patients with third line or greater metastatic pancreatic cancer.

Abstract

TPS463 Background: Pancreatic cancer has multiple mechanisms to prevent immune recognition that lead to the creation of an immune suppressive tumor microenvironment. We hypothesize that effective and sustained response against tumors requires a coordinated approach that: 1. reverses the immune-suppressive tumor microenvironment, 2. induces immunogenic tumor cell death and 3. reengages NK and T-cell tumor response against a 4. cascade of tumor antigens. To test this hypothesis, we developed the NANT Cancer Vaccine (NCV), which combines metronomic low-dose chemotherapy, radiotherapy and multifaceted immunotherapy. In proof-of-concept trials, the NCV was tested in 10 patients with 3rd-line or greater pancreatic cancer. These trials showed that the NCV could be safely administered in an outpatient setting, with AEs that were manageable by dose-reduction, and preliminary survival results that exceed the standard of care in this heavily-treated population. We believe these results warrant further research, and this abstract describes our newly-designed trial. Methods: A phase 1b, single-arm, open-label trial of the NANT Cancer Vaccine in patients with recurrent metastatic pancreatic cancer has been initiated. Treatment will occur in 3-week cycles of low-dose chemotherapy (aldoxorubicin, cyclophosphamide, oxaliplatin, nab-paclitaxel, 5-FU/L), antiangiogenic therapy (bevacizumab), SBRT, engineered allogeneic high affinity CD16 NK-92 cells (haNK), IL-15RαFc (N-803), adenoviral vector-based CEA vaccine (Ad-CEA), yeast vector-based RAS vaccine (Ye-RAS), and an IgG1 PD-L1 inhibitor, avelumab. The primary endpoint is incidence of treatment-related adverse events. Secondary endpoints include ORR, DCR, PFS, and OS. A maximum of 24 patients will be enrolled. Clinical trial information: NCT03586869.