GVAX Pancreas Vaccine (With CY) and CRS-207 With or Without Nivolumab

A Randomized Phase 2 Study of the Safety, Efficacy, and Immune Response of GVAX Pancreas Vaccine (With Cyclophosphamide) and CRS-207 With or Without Nivolumab in Patients With Previously Treated Metastatic Pancreatic Adenocarcinoma

The primary objective of this study is to compare the overall survival (OS) of subjects with previously treated metastatic pancreatic cancer treated with cyclophosphamide (CY)/nivolumab/GVAX pancreas vaccine followed by nivolumab/CRS-207 (Arm A) to subjects treated with CY/GVAX pancreas vaccine followed by CRS-207 (Arm B).

Inclusion Criteria:

• Age ≥18 years.
• Have histologically- or cytologically-proven adenocarcinoma of the pancreas. Patients with mixed histology will be excluded.
• Have metastatic disease.
• Have failed only 1 prior chemotherapy regimen for metastatic pancreatic cancer.
• Patients with the presence of at least one measurable lesion.
• Patients acceptance to have a tumor biopsy of an accessible lesion at baseline and on treatment if the lesion can be biopsied with acceptable clinical risk (as judged by the investigator).
• ECOG performance status 0 or 1.
• Life expectancy of greater than 3 months.
• Patients must have adequate organ and marrow function defined by study-specified laboratory tests.
• Must use acceptable form of birth control while on study.
• Ability to understand and willingness to sign a written informed consent document.

Exclusion Criteria:

• known history or evidence of brain metastases.
• Had surgery within the last 28 days
• Have received any non-oncology vaccine therapy used for prevention of infectious diseases including seasonal vaccinations within 28 days of study treatment.
• Prior treatment with anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CTLA4, GVAX or CRS-207
• Systemic steroids within the last 14 days
• Use more than 3 g/day of acetaminophen.
• Patients on immunosuppressive agents.
• Patients receiving growth factors within the last 14 days
• Known allergy to both penicillin and sulfa.
• Severe hypersensitivity reaction to any monoclonal antibody.
• Have artificial joints or implants that cannot be easily removed
• Have any evidence of hepatic cirrhosis or clinical or radiographic ascites.
• Have significant and/or malignant pleural effusion
• Infection with HIV or hepatitis B or C at screening
• Significant heart disease
• Conditions, including alcohol or drug dependence, intercurrent illness, or lack of sufficient peripheral venous access, that would affect the patient's ability to comply with study visits and procedures
• Unable to avoid intimate contact with another individual known to be at high risk of listeriosis (e.g., newborn infant, pregnant woman, HIV-positive individual) during the course of CRS-207 treatment until completion of antibiotic regimen.
• Are pregnant or breastfeeding.
• Have rapidly progressing disease