A Phase IIb, randomized, multicenter study of the efficacy of GVAX pancreas vaccine and CRS-207 compared to chemotherapy or to CRS-207 alone in adults with previously-treated metastatic pancreatic adenocarcinoma (eclipse study)

Abstract

Background: A heterologous prime‐boost vaccination strategy using GVAX pancreas vaccine and CRS‐207 is showing promise in patients with metastatic pancreatic adenocarcinoma (PDA). GVAX is composed of lethallyirradiated, allogeneic pancreatic cancer cells modified to express GM‐CSF and induces a broad response against multiple tumor antigens. GVAX is given with low‐dose cyclophosphamide (CY) to inhibit regulatory T cells. CRS‐207 is live‐attenuated Listeria monocytogenes engineered to express the tumor‐associated antigen mesothelin. CRS‐207 boosts responses against mesothelin and is unique in its capacity to stimulate both innate and adaptive immunity by activating T cells and NK cells. In a recently completed Phase II study, the CY/GVAX plus CRS‐207 combination resulted in statistically‐significant improvement of overall survival (OS) compared to CY/GVAX alone (Le, GI ASCO 2014). Methods: This is a Phase IIb study comparing CY/GVAX and CRS‐207 to chemotherapy or to CRS‐207 alone in adults with previously‐treated metastatic PDA. Subjects will be enrolled in two cohorts: 150 subjects into a primary cohort of patients with at least two prior treatment regimens for metastatic disease (3rd+ line) and 90 subjects into an exploratory cohort of patients with only one prior treatment regimen for metastatic disease (2nd line). Subjects will be randomized in a 1:1:1 ratio to receive either 2 doses of CY/GVAX and 4 doses of CRS‐207 (Arm A), 6 doses of CRS‐207 (Arm B) or physician's choice of select single‐agent chemotherapy (Arm C). The primary objective is to compare OS in the primary cohort between Arms A and C. Secondary/exploratory objectives include: comparison of OS in both primary and exploratory cohorts between all treatment arms, assessment of safety and clinical responses (tumor assessments and CA19‐9 levels) and correlation of Lm‐ and mesothelin‐specific T cell and other immunological responses with OS, progression‐free survival and best overall response.