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
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.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
17
Administered at a fixed dose of 240mg intravenously (IV) on Days 1, 15, 29 of each 42-day cycle, for up to 9 cycles.
Administered at a fixed dose of 75mg IV on Day 1 of Cycles 1 through 4. In the event of protocol-defined toxicity, the dose may be reduced to 50mg IV per protocol defined criteria.
Administered at a dose of 1.4 x 107 cells/kg IV on Day 1 of Cycle 1 and Day 15 of Cycle 2.
Scripps Clinic Torrey Pines
La Jolla, California, United States
RECRUITINGOverall Response Rate (ORR)
ORR, defined as the proportion of participants whose best overall response (BOR) is either Complete Response (CR) or Partial Response (PR) per RECIST v1.1.
Time frame: From enrollment until first documented disease progression or end of study treatment (up to approximately 12 months).
Overall response rate in liver metastasis (ORLM)
ORLM, defined as the proportion of participants whose best overall response (BOR) in liver target lesions is Complete Response (CR-Liver) or Partial Response (PR-Liver) per RECIST v1.1.
Time frame: From enrollment until first documented disease progression or end of study treatment (up to approximately 12 months).
Progression free survival (PFS) at 6 months (PFS6)
Proportion of participants alive and progression-free at 6 months
Time frame: At 6 months from enrollment
Progression Free Survival (PFS) at 12 months (PFS12)
Proportion of participants alive and progression-free at 12 months
Time frame: At 12 months from enrollment
Overall Survival (OS)
Defined as the time interval from date of enrollment to death from any cause.
Time frame: From enrollment until death from any cause
Time to Tumor Response (TTR)
Defined as the time interval from date of enrollment to date of the first documented CR or PR per RECIST v1.1.
Time frame: From enrollment until first documented complete (CR) or partial response (CR) per RECIST v1.1 (up to approximately 12 months).
Duration of Response (DOR)
Defined as the time interval from date of first documented CR or PR to the earliest date of documented tumor progression or death from any cause, whichever occurs first.
Time frame: From date of first documented CR or PR per RECIST v1.1 to date of disease progression or death from any cause, whichever occurs first (up to approximately 12 months).
Biochemical response (CEA and/or CA 19-9)
Defined as ≥ 50% reduction from baseline in serum CEA and/or CA 19-9 levels.
Time frame: From enrollment until completion of biomarker assessments (up to approximately 12 months).
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.