A phase IIb, randomized, controlled, multicenter, open-label study of the efficacy and immune response 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).
TPS489 Background: A prime-boost vaccination strategy using GVAX pancreas vaccine and CRS-207 is showing activity in patients with metastatic pancreatic adenocarcinoma (PDA). GVAX is composed of lethally-irradiated, allogeneic pancreatic cancer cells modified to express GM-CSF. GVAX induces a response against multiple tumor antigens and is given after 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 stimulates both innate and adaptive immunity by activating T cells and NK cells. Results from a phase 2 study demonstrated CY/GVAX plus CRS-207 improved overall survival (OS) compared to CY/GVAX alone (p-value<0.05; Le, GI ASCO 2014). Methods: This is a phase 2b study comparing CY/GVAX and CRS-207 to chemotherapy or to CRS-207 alone in patients with previously-treated metastatic PDA. Patients will be enrolled in two cohorts: 150 patients into a primary cohort of patients with at least two prior chemotherapy regimens for metastatic disease (third + line) and 90 patients into an exploratory cohort of patients with only one prior chemotherapy regimen for metastatic disease (second line). Patients will be randomized in a 1:1:1 ratio to receive 2 doses of CY/GVAX and 4 doses of CRS-207 (Arm A), six doses of CRS-207 (Arm B) or physician’s choice of single-agent chemotherapy (Arm C). The primary objective is to compare OS between Arms A and C in the primary cohort. 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 clinical responses. Updated enrollment will be reported. (Sponsor: Aduro BioTech, Inc.; NCT02004262). Clinical trial information: NCT02004262.