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

Prior treatment

• 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.
• Prior tissue or organ allograft or allogeneic bone marrow transplantation.
• History of encephalitis, meningitis, or uncontrolled seizures in the year prior to informed consent.

Other illness

• Hypersensitivity reaction to any monoclonal antibody.
• Has uncontrolled intercurrent acute or chronic medical illness.
• Has an active known or suspected autoimmune disease.
• History of interstitial lung disease.
• Significant heart disease
• Infection with HIV or hepatitis B or C at screening.
• Has an active infection.
• 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.

Other

• Has a diagnosis of immunodeficiency.
• Requires daily supplemental oxygen
• Requires daily supplemental oxygen.
• Unable to have blood drawn.
• Woman who are pregnant or breastfeeding.

• 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.