Phase II, randomized study of GVAX pancreas and CRS-207 immunotherapy in patients with metastatic pancreatic cancer: Clinical update on long term survival and biomarker correlates to overall survival.

261 Background: In a phase 2a randomized study, metastatic pancreatic ductal adenocarcinoma (PDA) patients treated sequentially with two vaccine-based immunotherapies showed extended overall survival (OS) with tolerable side effects. Treatment included low-dose cyclophosphamide (CY) to inhibit T-regulatory cells prior to GVAX, an irradiated GM-CSF-secreting allogeneic PDA cell vaccine, which activates a broad antigenic response, followed by CRS-207, a live-attenuated, mesothelin-expressing Listeria monocytogenes vaccine which stimulates innate and adaptive immunity. Methods: Patients were enrolled with metastatic 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). PBMC and serum were collected over the course of treatment for immune and biomarker analyses. CyTOF, ELISPOT, and luminex were used to identify biomarker correlates of OS. Result...