Temozolomide, Cisplatin, and Nivolumab in People With Colorectal Cancer

Inclusion Criteria: * Subject or legally authorized representative is willing and able to provide written informed consent/assent for the trial. * Histologically- or cytologically- confirmed colorectal adenocarcinoma. * Locally advanced unresectable or metastatic CRC. * Undergone testing for MSI/dMMR and determined to be MSS or MMR proficient. * Undergone testing for BRAF and POLE and determined to be wild type. * Subjects must be refractory to, or intolerant of, at least 2 lines of standard chemotherapy, according to NCCN guidelines for patients eligible for intensive therapy, or have received prior FOLFOXIRI. Patients are considered refractory if progressed within 3 months of last dose, or within 6 months of completing adjuvant FOLFOX/CAPEOX. At a minimum, such therapies should include oxaliplatin, irinotecan and a fluoropyrimidine. * At least one index lesion which is measurable based on RECIST 1.1. * Be ≥ 18 years of age on day of signing informed consent. * Consent for use of archival tissue and blood draws for research purposes. * Have an ECOG performance status of 0 or 1. * Demonstrate adequate organ function as defined in Table 6.1, all screening labs should be performed within 28 days of treatment initiation. * Adequate organ function, defined as: * Absolute Neutrophil Count ≥ 1,500/mcL. * Platelet count ≥ 100,000/mcL. * Serum creatinine ≤ 1.5 x ULN or CrCl ≥60 mL/min for subjects with creatinine levels \>1.5 ULN. * WBC ≥ 2000/μL * Hemoglobin ≥ 9.0 g/dL …