Platform Study of Immunotherapy Combinations in Colorectal Cancer Liver Metastases
The goal of this clinical trial is to to learn about different combinations of immunotherapy in patients with colorectal cancer whose cancer has spread to their liver and are planning to have surgery to remove tumor metastases from their liver. The main questions it aims to answer are:

whether these combinations of immunotherapy change the tumor microenvironment in the liver
whether these combinations of immunotherapy are safe and effective when used in colorectal cancer with liver metastases

Participants will be randomly assigned to one of the following:

Botensilimab and balstilimab
Botensilimab, balstilimab, and AGEN1423
Botensilimab, balstilimab, and radiation

Participants will be asked to come in to receive drug infusions (and radiation, if applicable) before and after their surgical resection. Participants will be followed for up to 2 years.
- EligibilityCriteria: Inclusion Criteria:  Diagnosis of metastatic colorectal adenocarcinoma with liver metastases Participant must be planning to undergo a surgical resection of their liver metastases. Tumor is non-MSI-H/dMMR Presence of measurable disease Participants must be willing to consent to additional molecular analyses of tumor samples removed during surgery for research purposes Women of childbearing potential (WOCBP), or anyone with a uterus, must not be pregnant or breastfeeding. All participants of childbearing potential must agree to use highly effective contraception during this study Participants may not receive chemotherapy, growth factor support, transfusions, or albumin administration within 14 days of start of study treatment.  Exclusion Criteria:  Not eligible for surgery Any medical condition such as uncontrolled infection, uncontrolled diabetes mellitus or cardiac disease which, in the opinion of the treating physician, would make this protocol unreasonably hazardous for the patient. Previous allogeneic tissue/organ transplant Previously received PD-1, PD-L1, or CTLA-4 therapy including experimental immunologic agents Participants must not have any contraindications to immune checkpoint inhibitors Participants must not have active autoimmune disease that has required systemic treatment within 2 years prior to registration. Some exceptions are allowed - HealthyVolunteers: No - Gender: All - MinimumAge: 18 Years - StdAgeList: Adult, Older Adult