Combination Immunotherapy in Colorectal Cancer

This is a pilot study to see whether a combination of two investigational drugs that target the immune system can be given to people with colorectal cancer before surgically removing the tumor. This study is also being done to see what side effects this combination of drugs has and what effect they have on colorectal cancer. The two monoclonal antibodies are balstilimab, a programmed cell death protein 1 (PD-1) inhibitor, and botensilimab, a cytotoxic T lymphocyte-associated protein 4 (CTLA-4) inhibitor. This study has 3 cohorts. Participants in Cohort A will receive a total of 2 doses of balstilimab and a single dose of botensilimab, both given intravenously (IV), before surgery. Participants in Cohort B and C will receive a total of 4 doses of balstilimab and a single dose of botensilimab, both given intravenously (IV), before surgery. Participants in Cohort C must have dMMR/MSI-High colorectal cancer.

Inclusion Criteria: * 18 years of age or older * Histologically, cytologically, or clinically confirmed adenocarcinoma of the colon or rectal cancer as long as there is no plans for neoadjuvant radiation for the patients with rectal cancer. Note: patients can enroll in cohort B while awaiting mismatch repair testing results. If noted to be dMMR/MSI-High, they would be still considered evaluable and moved to cohort C. * If capable of becoming pregnant, or getting someone else pregnant, must be willing to use highly effective contraception from Screening period through 90 days following the last dose of study drug Exclusion Criteria: * Metastatic cancer (cancer that has spread to other parts of the body) * Previous treatment with immune checkpoint inhibitors targeting CTLA-4, PD-1 or PD-L1 * Currently participating in another study and receiving a study drug * History of severe allergic reactions to immunotherapies * Pregnant or breastfeeding * Active infection requiring treatment * On immunosuppressive medications * Active cardiovascular disease, such as stroke or myocardial infarction within 6 months of enrollment, unstable angina, congestive heart failure, or serious uncontrolled cardiac arrhythmia requiring medication that may prevent surgery Participants in Cohort C must be dMMR/MSI-High.