Study of Nivolumab and Relatlimab in Patients With Microsatellite Stable (MSS) Advanced Colorectal Cancer

Inclusion Criteria: * Age ≥18 years. * ECOG performance status 0 or 1 * Have metastatic or locally advanced microsatellite stable (MSS) colorectal adenocarcinoma. * Cohort A: Primary lesion has a composite PD-L1/Mucin (CPM) score ≥ 15%. * Cohort B: Primary lesion has a composite PD-L1/Mucin (CPM) score \< 15%. * Cohort C: Prior surgical resection of primary tumor. Prospective biomarker evaluation not required. * Must have received at least one chemotherapy regimen. * Patients with the presence of at least one measurable lesion using RECIST 1.1. * Patients must have available archival tissue from the surgical resection of their primary tumor. * Patient's acceptance of tumor biopsies. * Life expectancy of greater than 3 months. * Patients must have adequate organ and marrow function defined by study - specified laboratory tests. * Documented LVEF ≥ 50% - 6 month prior to drug administration. * 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. Patients with previously treated brain metastases may participate if they are stable for 4 weeks prior to beginning treatment, have no new or enlarging brain metastases, and are not using steroids for at least 1 week prior to initiation of study treatment. * Require any antineoplastic therapy. * History of prior treatment with anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CTLA-4, or anti-Lag-3 antibodies. * Had chemotherapy, radiation, or steroids within 14 days prior to study treatment. * Had any cytotoxic drug within 4 weeks prior to initiation of study treatment. * Hypersensitivity reaction to any monoclonal antibody. * Has uncontrolled intercurrent acute or chronic medical illness. * Has an active known or suspected autoimmune disease. * Has a diagnosis of immunodeficiency. * Prior tissue or organ allograft or allogeneic bone marrow transplantation. * Requires daily supplemental oxygen * History of interstitial lung disease. * Requires daily supplemental oxygen. * Significant heart disease * History of encephalitis, meningitis, or uncontrolled seizures in the year prior to informed consent. * Infection with HIV or hepatitis B or C at screening. * Has an active infection. * Unable to have blood drawn. * Patient with uncontrolled intercurrent illness including, but not limited to, uncontrolled infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements. * Woman who are pregnant or breastfeeding.