BAL/BOT/agenT-797 in pMMR CRC With Liver Metastases

This is a Phase II, single-arm, investigator-sponsored clinical trial evaluating the safety and efficacy of the combination of balstilimab (anti-PD-1), botensilimab (Fc-enhanced anti-CTLA-4), and agenT-797 (allogeneic invariant natural killer T \[iNKT\] cell therapy) in patients with previously treated microsatellite stable (pMMR) metastatic colorectal cancer with liver metastases. Patients with pMMR/MSS metastatic colorectal cancer derive limited benefit from currently available immunotherapy approaches. The liver tumor microenvironment is associated with immune tolerance and resistance to checkpoint blockade. This study is designed to evaluate whether combining dual checkpoint inhibition with cellular therapy can enhance anti-tumor immune responses and improve clinical outcomes in this population. The primary objective of the study is to evaluate the objective response rate (ORR) as assessed by RECIST v1.1. Secondary objectives include evaluation of safety and tolerability, duration of response (DOR), progression-free survival (PFS), and overall survival (OS). Exploratory objectives include assessment of biomarkers such as circulating tumor DNA (ctDNA), tumor markers, and immune-related correlates. Participants will receive combination treatment in 42-day cycles for up to nine cycles or until disease progression, unacceptable toxicity, withdrawal of consent, or investigator decision. Balstilimab and botensilimab will be administered in combination with agenT-797 according to the study protocol. Tumor assessments will be performed using CT or MRI at regular intervals to evaluate response per RECIST v1.1. Safety will be monitored throughout the study through assessment of adverse events, laboratory evaluations, and clinical examinations, with particular attention to immune-mediated and cytokine-related toxicities. Blood samples will be collected for safety monitoring and exploratory biomarker analyses, including ctDNA and immune profiling. Archival tumor tissue will be collected when available, and on-study biopsies may be obtained to support correlative research. Following completion of study treatment, participants will undergo a safety follow-up period and will be followed for survival at regular intervals.