A Single-Arm, Phase II Study Evaluating Combination Balstilimab Plus Botensilimab With AgenT-797 in Previously Treated Patients With pMMR Metastatic CRC With Liver Metastases
The goal of this clinical trial is to learn whether the combination of balstilimab, botensilimab, and agenT-797 is safe and effective in treating adults with previously treated metastatic colorectal cancer that is microsatellite stable (pMMR) and has spread to the liver. The main questions it aims to answer are: * What proportion of participants experience tumor shrinkage (objective response rate) based on imaging assessments? * What side effects occur with this combination treatment, including immune-related and cytokine-related reactions? All participants in this study will receive the combination treatment. There is no comparison group. Participants will: * Receive balstilimab, botensilimab, and agenT-797 in repeating 42-day treatment cycles * Undergo imaging scans (such as CT or MRI) to assess tumor response * Have blood samples collected to monitor safety and evaluate biomarkers * Provide tumor tissue samples for research * Be monitored for side effects throughout the study * Participate in follow-up visits to assess survival after treatment completion
• Adults ≥18 years of age with histologically confirmed metastatic colorectal cancer with liver metastases, including evidence of active liver disease if previously treated locally
• At least one measurable lesion per RECIST v1.1, with ≥1 target lesion in the liver
• Tumor confirmed as microsatellite stable (MSS)/proficient mismatch repair (pMMR) per a FDA-approved assay (Caris MI Cancer Seek®, FoundationOne® CDx, or Tempus xT CDx).
• Received ≥1 prior line of systemic therapy including fluorouracil, oxaliplatin, and irinotecan (not necessarily in combination), and prior EGFR inhibitor or bevacizumab if eligible, unless contraindicated
• ECOG performance status 0-1 and life expectancy ≥12 weeks
• Adequate organ and marrow function:
‣ ANC ≥1.5 × 10⁹/L
⁃ Platelets ≥100 × 10⁹/L
⁃ Hemoglobin ≥ 9 g/dL
⁃ AST/ALT ≤2.5 × ULN
⁃ Total bilirubin ≤1.5 × ULN
⁃ Creatinine clearance ≥ 40 mL/min, as measured or calculated per local institutional standards.
⁃ Albumin ≥3 g/dL
⁃ PT/PTT ≤1.5 × ULN
• Willing and able to provide written informed consent
• Negative pregnancy test for women of childbearing potential
• Agreement to use effective contraception during study participation