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

April 21, 2026 updated by: Darren Sigal, MD

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

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

Detailed Description

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

Enrollment (Estimated)

17

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • 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)
  • 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 ≥8 g/dL
    • AST/ALT ≤2.5 × ULN
    • Total bilirubin ≤1.5 × ULN
    • Creatinine clearance ≥30 mL/min
    • 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

Exclusion Criteria:

  • Tumor is dMMR/MSI-high
  • Prior treatment with PD-1, PD-L1, CTLA-4 inhibitors, or other immunotherapy agents
  • Evidence of bowel obstruction, impending obstruction, or recent obstruction (within 3 months)
  • Refractory ascites requiring frequent paracentesis or recent escalation of diuretics
  • Clinically significant cardiovascular disease (e.g., recent myocardial infarction or stroke, unstable angina, NYHA class ≥III heart failure, uncontrolled arrhythmias) or QTc >480 ms
  • Active or untreated brain metastases or leptomeningeal disease
  • Concurrent malignancy requiring treatment or active within 2 years (with protocol-specified exceptions)

  • Receipt of prior anti-cancer therapy within protocol-defined washout periods, including:

    • Cytotoxic, targeted therapy or other investigational therapy within 3 weeks.
    • Monoclonal antibodies, antibody-drug conjugates, radioimmunoconjugates, or similar therapy, within 4 weeks, or 5 half-lives, whichever is shorter.
    • Small molecules/tyrosine kinase inhibitors within 2 weeks or less than 5 circulating half-lives of investigational drug.
  • Known hypersensitivity to study drugs or excipients
  • History of or active interstitial lung disease or pneumonitis requiring systemic steroids
  • Prior allogeneic transplant (organ, stem cell, or bone marrow)
  • Active or recent autoimmune disease requiring systemic treatment
  • Requirement for systemic corticosteroids (>10 mg prednisone equivalent) or other immunosuppressive therapy within defined windows
  • Active infection, including HIV, HTLV, HBV, HCV, or other infections requiring systemic therapy
  • Recent SARS-CoV-2 infection within protocol-defined timeframe
  • Uncontrolled hypertension, significant proteinuria (UPCR ≥1 g/g), or other clinically significant uncontrolled medical conditions
  • Non-healing wounds, active bleeding, or uncontrolled thyroid dysfunction
  • Psychiatric or substance use disorders that may interfere with study participation
  • Receipt of live or attenuated vaccines within 30 days prior to treatment and while participating in the study
  • Pregnant or breastfeeding women, or those planning pregnancy during the study

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Treatment arm
balstilimab (BAL) + botensilimab (BOT) + agenT-797
Drug: Balstilimab (BAL)
Administered at a fixed dose of 240mg intravenously (IV) on Days 1, 15, 29 of each 42-day cycle, for up to 9 cycles.
Other Names:
  • AGEN2034
Drug: Botensilimab (BOT)
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.
Other Names:
  • AGEN1181
Drug: agenT-797
Administered at a dose of 1.4 x 107 cells/kg IV on Day 1 of Cycle 1 and Day 15 of Cycle 2.
Other Names:
  • allo-INKTs

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Overall Response Rate (ORR)
Time Frame: From enrollment until first documented disease progression or end of study treatment (up to approximately 12 months).
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.
From enrollment until first documented disease progression or end of study treatment (up to approximately 12 months).

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Overall response rate in liver metastasis (ORLM)
Time Frame: From enrollment until first documented disease progression or end of study treatment (up to approximately 12 months).
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.
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)
Time Frame: At 6 months from enrollment
Proportion of participants alive and progression-free at 6 months
At 6 months from enrollment
Progression Free Survival (PFS) at 12 months (PFS12)
Time Frame: At 12 months from enrollment
Proportion of participants alive and progression-free at 12 months
At 12 months from enrollment
Overall Survival (OS)
Time Frame: From enrollment until death from any cause
Defined as the time interval from date of enrollment to death from any cause.
From enrollment until death from any cause
Time to Tumor Response (TTR)
Time Frame: From enrollment until first documented complete (CR) or partial response (CR) per RECIST v1.1 (up to approximately 12 months).
Defined as the time interval from date of enrollment to date of the first documented CR or PR per RECIST v1.1.
From enrollment until first documented complete (CR) or partial response (CR) per RECIST v1.1 (up to approximately 12 months).
Duration of Response (DOR)
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).
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.
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)
Time Frame: From enrollment until completion of biomarker assessments (up to approximately 12 months).
Defined as ≥ 50% reduction from baseline in serum CEA and/or CA 19-9 levels.
From enrollment until completion of biomarker assessments (up to approximately 12 months).

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Changes in circulating tumor DNA (ctDNA) from baseline during study treatment in responders and non-responders, per RECIST1.1.
Time Frame: From baseline through post-baseline ctDNA assessments up to End of Treatment (approximately 12 months).
Absolute and percent change from baseline ctDNA levels at scheduled post-baseline assessments (Cycle 3/Day 1, Cycle 5/Day 1, and End of Treatment).
From baseline through post-baseline ctDNA assessments up to End of Treatment (approximately 12 months).
Immunophenotyping and Immune Profiling of Peripheral Blood and Tumor Microenvironment (TME)
Time Frame: From baseline through longitudinal immune profiling assessments during study treatment and at End of Treatment (up to approximately 12 months).
From baseline through longitudinal immune profiling assessments during study treatment and at End of Treatment (up to approximately 12 months).

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Darren Sigal, MD

Collaborators

Scripps Health

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

June 1, 2026

Primary Completion (Estimated)

September 1, 2028

Study Completion (Estimated)

December 1, 2028

Study Registration Dates

First Submitted

April 15, 2026

First Submitted That Met QC Criteria

April 21, 2026

First Posted (Actual)

April 24, 2026

Study Record Updates

Last Update Posted (Actual)

April 24, 2026

Last Update Submitted That Met QC Criteria

April 21, 2026

Last Verified

April 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • SC-CRC-IST-01

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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