Combination of balstilimab, botensilimab, and agenT-797 in pMMR colorectal cancer with liver metastases

Is this trial a fit for you?

A plain-English reading of the study's rules. Only the study team can confirm whether you qualify.

What this trial studies

This Phase 2, single-arm study evaluates safety and effectiveness of balstilimab (anti-PD-1), botensilimab (anti-CTLA-4), and agenT-797 (iNKT cell therapy) in adults with previously treated MSS/pMMR metastatic colorectal cancer with liver metastases. Participants receive the combination in 42-day cycles for up to nine cycles, with imaging to track tumor response and blood/tissue samples collected for safety monitoring and biomarker research. Primary outcome is objective response rate by RECIST v1.1, while secondary outcomes include safety, duration of response, progression-free survival, and overall survival, plus exploratory biomarker analysis. The study has no control arm and all participants receive the same treatment regimen. Sites are at Scripps Clinic Torrey Pines, under lead sponsor Darren Sigal, MD, in collaboration with Scripps Health.

Why it matters

Who can join: the full rules

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) 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

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

Where it's running

• Scripps Clinic Torrey Pines
  La Jolla, California, United States Recruiting

Similar studies

Other studies for the same condition or treatment. Recruiting studies are listed first.

• Botensilimab + Balstilimab before surgery for early MSS rectal cancer

  This study tests whether giving a single dose of botensilimab followed by balstilimab can shrink MSS/pMMR early rectal tumors so some patients can avoid surgery.

  Recruiting at 2 sites Phase 2 Dana-Farber Cancer Institute · Boston, Massachusetts and 2 other locations · NCT07735624

• Neoadjuvant Botensilimab and Balstilimab for Advanced Resectable Colorectal Cancer

  This phase 2 trial tests whether giving botensilimab and balstilimab before surgery can help patients with advanced, resectable colorectal cancer see better outcomes.

  Recruiting at 11 sites Phase 2 City of Hope Medical Center · Goodyear, Arizona and 10 other locations · NCT07595874

• Combining botensilimab and balstilimab after standard treatment for colorectal cancer

  This phase 2 trial tests whether giving botensilimab and balstilimab after standard therapy can clear detectable ctDNA in adults with stage II/III colorectal cancer.

  Recruiting at 2 sites Phase 2 National Cancer Institute (NCI) · New Orleans, Louisiana and 1 other locations · NCT07551596

• Neoadjuvant immunotherapy with botensilimab and balstilimab for high-risk non-metastatic clear cell RCC

  This trial tests whether giving botensilimab and balstilimab before kidney tumor surgery is safe and helps patients with high‑risk non‑metastatic clear cell RCC proceed to nephrectomy.

  Recruiting at 5 sites Phase 2 National Cancer Institute (NCI) · Irvine, California and 4 other locations · NCT07516366

• Botensilimab plus balstilimab followed by balstilimab for colorectal cancer with detectable ctDNA after surgery and chemotherapy

  This trial tests whether giving botensilimab with balstilimab, then continuing balstilimab alone, helps people with microsatellite-stable colorectal cancer or colorectal liver metastases who still have detectable ctDNA after surgery and chemotherapy.

  Recruiting at 7 sites Phase 2 Memorial Sloan Kettering Cancer Center · Basking Ridge, New Jersey and 6 other locations · NCT07227636

• Botensilimab and balstilimab plus SBRT for liver‑metastatic colorectal cancer

  This tests whether adding two immune drugs, botensilimab and balstilimab, to focused liver radiation (SBRT) can help people with chemorefractory, non‑MSI‑high colorectal cancer that has spread to the liver.

  Recruiting Early Phase 1 Massachusetts General Hospital · Boston, Massachusetts · NCT07128355

How to take part

1. Review the eligibility criteria above with your treating physician.
2. Check the official listing on ClinicalTrials.gov for the latest contact details and recruitment status.
3. Contact the study coordinator or principal investigator to ask for pre-screening. Pre-screening is free and never obligates you to enroll.