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.