Study of Pembrolizumab in Combination With Chemotherapy for Patients With Advanced Colorectal Cancer

This is a multi-institutional, single arm, open-label, phase II study, including a safety run-in cohort. No randomization or blinding involved.

OUTLINE: This is a multi-center study. INVESTIGATIONAL TREATMENT: mFOLFOX6 Treatment D1 and D15 (Cycle = 28 days) * Oxaliplatin 85 mg/m2 IV with * Leucovorin 400 mg/m2 IV followed by * 5FU 400 mg/m2 bolus and then 2400 mg/m2 via continuous infusion Pembrolizumab (MK-3475) IV over 30 minutes every 3 weeks SAFETY RUN-IN COHORT: The safety run-in cohort will include 6 subjects treated with 200 mg (fixed) IV infusion of pembrolizumab (MK-3475) every 3 weeks plus standard-dose mFOLFOX6 given every 2 weeks. These first 6 subjects will be followed for 4 weeks for dose limiting toxicities (DLT) before enrolling an additional 24 patients. If a DLT is observed in no more than 1 of 6 subjects, the trial will continue with enrolling subjects to the remainder of the phase II portion of the study. Otherwise, 6 additional subjects will be enrolled at dose level -1. If no more than one DLT is observed, then phase II will enroll subjects at dose level -1 for the total expected number of accrual. Disease evaluation every 8 weeks or after every 2 cycles Demonstrate adequate organ function as defined by the following laboratory values at study entry. All screening labs should be performed within 14 days prior to registration for protocol therapy. Hematopoietic: * Hemoglobin ≥ 9 g/dL (transfusions are acceptable) * Absolute neutrophil count (ANC) ≥ 1.5 × 10\^9/L * Platelets ≥ 100 × 10\^9/L Renal: * Serum creatinine ≤ 1.5 × upper limit of normal (ULN), or measured or calculated creatinine clearance (estimated by Cockcroft-Gault formula below or measured) ≥ 50 mL/min Hepatic: * Serum total bilirubin ≤ 1.5 × ULN * Aspartate aminotransferase (AST, SGOT) and alanine aminotransferase (ALT, SGPT) ≤ 3 × ULN, unless evidence of liver metastases, then AST/ALT ≤ 5 x ULN