Interim safety and efficacy analysis of a phase II, randomized study of GVAX pancreas and CRS-207 immunotherapy in patients with metastatic pancreatic cancer.

4040^ Background: GVAX is composed of GM-CSF-secreting allogeneic pancreas cancer cell lines and administered with low-dose cyclophosphamide (CY) to inhibit regulatory T cells. In prior studies, GVAX induced mesothelin-specific T cell responses that correlated with survival. CRS-207 is a live-attenuated Listeria monocytogenes engineered to express human mesothelin. CRS-207 stimulates potent innate and adaptive immunity and has shown synergy with GVAX in mouse tumor models. Anecdotal survival benefit was observed in the CRS-207 phase I study in patients who received prior GVAX. Methods: Patients were enrolled with metastatic pancreatic ductal adenocarcinoma (PDA) who received or refused ≥ 1 prior chemotherapy, had ECOG ≤ 1 and adequate organ function. Patients were randomized 2:1 to receive 2 doses of CY/GVAX followed by 4 doses of CRS-207 (Arm A) or 6 doses of CY/GVAX (Arm B) every 3 weeks. Clinically stable patients were offered additional 20-week courses. The primary endpoint was comparison of OS betwee...