Combination Immunotherapy for the Treatment of Chemotherapy-refractory Metastatic MSS CRC

Inclusion Criteria: * Patients must have a pathologically confirmed diagnosis of non-MSI-H/pMMR CRC. * Patients must have progressed (clinically or radiographically) on or after standard chemotherapy, including fluoropyrimidines, oxaliplatin, and irinotecan, or are intolerant to standard chemotherapy. Patients may have received, if eligible, anti-VEGF or anti-EGFR antibodies in combination with chemotherapy. * Patients must have at least 1 measurable target lesion at baseline ≥ 10mm in the longest diameter. * Patient must be willing and able to provide blood samples (6 heparinized, and two streck tubes, roughly 70 - 80 mL) at the time points indicated in the Study Calendar. * Patients must have at least 1 lesion suitable for core needle biopsies. * Patients must be willing and able to have core needle biopsies, if clinically feasible (Goal 3-6 biopsies, final number to be determined by the interventionalist performing the procedure as safe), of tumor prior to initiation of study drug. Should patients undergo pre-treatment or on-treatment biopsy procedure and inadequate number of biopsies are obtained, they may proceed with initiation/continuation of treatment at the discretion of the investigator and treating physician. * Age ≥ 18 years. * ECOG Performance Status 0-1 (Karnofsky ≥60%, see https://ecog-acrin.org/resources/ecog-performance-status/). o Patients with performance status \>1 carrying long-term disability (such as cerebral palsy) where the disability is not acute no…