Nivolumab and Metformin in Patients With Treatment Refractory MSS Colorectal Cancer

PRIMARY OBJECTIVE: I. To evaluate the effect of nivolumab and metformin combination on the overall response rate (ORR) as assessed by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. SECONDARY OBJECTIVES: I. To determine the effect of nivolumab and metformin combination on clinical outcomes, progression free survival and overall survival, and biochemical response (CEA). II. To compare the effect of nivolumab and metformin combination on immune and metabolic biomarkers in the tumor microenvironment and systemic circulation (pre and post treatment paired biopsies required). OUTLINE: Patients receive metformin PO BID starting on day 1. After 14 days of metformin only period patients also receive nivolumab IV every 4 weeks starting on day 15. Courses repeat every 28 days for up to 2 years in the absence of disease progression, unacceptable toxicity or consent withdrawal After completion of study treatment, patients are followed up at day 30 and then periodically thereafter.