NCT07128355

Botensilimab, Balstilimab, and SBRT in Colorectal Cancer

A Pilot Study of Botensilimab and Balstilimab and SBRT in Non-MSI-H or pMMR Colorectal Cancer With Liver Metastasis

• Status: Not Yet Recruiting
• Phase: EARLY_Phase 1
• Study type: Interventional
• Enrollment: 15 (estimated)
• Sponsor: Massachusetts General Hospital · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This is a single-arm pilot feasibility study evaluating the combination of Botensilimab and Balstilimab with Radiation Therapy (RT) in Non-Microsatellite Instability High (MSI-H) or Proficient Mismatch Repair (pMMR) chemorefractory colorectal cancer (CRC) with liver metastasis.

Detailed description

In this open-label study, the investigators propose to use standard of care (SOC) radiation (Stereotactic Body Radiation Therapy (SBRT)) to control the liver lesions in combination with investigational dual checkpoint inhibitors, botensilimab (AGEN1181) and balstilimab (AGEN2034). Initially, 5 patients will be enrolled in a lead-in cohort and assessed for dose-limiting toxicity (DLT) related to radiation during Cycle 1. If DLT are observed in 2 or more of the first 5 patients, the protocol will be stopped early. If DLT were observed in 0 or 1 of the first 5 patients during the lead-in, enrollment will be expanded to a total of 15 patients. After screening, participants will receive SOC SBRT for 2-3 weeks, and botensilimab + balstilimab for up to 24 weeks followed by balstilimab alone for 14 additional 6-week cycles, for a total treatment time of up to 108 weeks. Participants will be followed for 1 year.

Conditions

• Non-MSI-H or pMMR Colorectal Cancer With Liver Metastasis

Interventions

Type	Name	Description
RADIATION	Stereotactic Body Radiation Therapy (SBRT)	Starting on Day 1 participants will have 2-4 treatments per week for about 2 weeks, with no more than 2 days in a row. This is expected to last about 2 weeks but could last up to 3 weeks.
DRUG	Botensilimab	Administered once every 6 weeks by intravenous infusion over about 30 minutes, on Day 1 of Cycles 1-4 (six-week cycles). Administered 30 minutes after balstilimab.
DRUG	Balstilimab	Administered once every 2 weeks by intravenous infusion over about 30 minutes, starting on Day 1 of Cycle 1 and continuing for 4 six-week cycles (with botensilimab) followed by up to 14 six-week cycles of balstilimab alone. Participants will receive balstilimab for a total of 18 six-week cycles.

Timeline

• Start date: 2026-06-01
• Primary completion: 2027-01-01
• Completion: 2027-09-01
• First posted: 2025-08-18
• Last updated: 2026-04-09

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study
• FDA-regulated device study