Botensilimab, Balstilimab, and SBRT in Colorectal Cancer

NCT07128355 | Not Yet Recruiting Early Phase 1 DMC FDA Drug FDA Device

• 1 other identifier: 25-495
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

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

Keywords

colorectal cancer; colorectal cancer with liver metastasis; Non-MSI-H or pMMR Colorectal Cancer

Outcome Measures

Primary Outcomes (1)

• Incidence of dose limiting radiation-related toxicities

  Dose limiting radiation-related toxicities will be assessed by CTCAE v6.0. A dose limiting toxicity (DLT) will be defined as any patient who can't complete all radiation therapy (RT) fractions within 2-3 weeks for pre-specified toxicity or lab values attributable to radiation therapy, or development of RT-related toxicities within 30 days of completion of RT. Participants will be evaluable for DLT once they start protocol therapy.

  Day 1 of treatment through 30 days after completion of radiation therapy (radiation therapy is 2-3 weeks), up to 60 days.

Secondary Outcomes (5)

• Response rate of in-field radiated hepatic lesion(s)

  Screening through end of Cycle 18 (each cycle is 6 weeks), up to 108 weeks.

• Response rate of extrahepatic lesion(s)

  Screening through end of Cycle 18 (each cycle is 6 weeks), up to 108 weeks.

• Overall Survival (OS)

  Registration through 160 weeks (108 weeks of treatment + 1 year follow-up)

• Progression-Free Survival (PFS)

  Registration through up to 108 weeks of treatment

• Disease Control Rate (DCR)

  Day 1 through up to 108 weeks.

Study Arms (1)

Stereotactic Body Radiation Therapy (SBRT) + Botensilimab + Balstilimab

EXPERIMENTAL

Participants will receive: * standard of care (SOC) SBRT for 2-3 weeks (Cycle 1); * botensilimab, on Day 1 of 6-week cycles (Cycles 1-4); * balstilimab, once every 2 weeks (Cycles 1-18, 6-week cycles).

Radiation: Stereotactic Body Radiation Therapy (SBRT); Drug: Botensilimab; Drug: Balstilimab

Interventions

Botensilimab DRUG

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.

Also known as: AGEN1181

Stereotactic Body Radiation Therapy (SBRT) + Botensilimab + Balstilimab

Balstilimab DRUG

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.

Also known as: AGEN2034

Stereotactic Body Radiation Therapy (SBRT) + Botensilimab + Balstilimab

Stereotactic Body Radiation Therapy (SBRT) RADIATION

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.

Also known as: SBRT

Stereotactic Body Radiation Therapy (SBRT) + Botensilimab + Balstilimab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participants must have histologically or cytologically confirmed adenocarcinoma of colorectal origin.
• MSS or pMMR status confirmed by IHC or PCR.
• Must have at least 1 measurable (≥ 1 cm) previously unirradiated hepatic lesion amenable to ablative RT and meeting dose constraints. A maximum of 5 hepatic lesions are allowed provided all are amenable to ablative RT and meet dose constraints. Must have at least 1 other unirradiated measurable (≥ 1cm) extrahepatic lesion, outside of RT field. Patients should ideally have a second unirradiated lesion, outside of RT field, that would be amenable for paired biopsies.
• Must have received or confirmed intolerance to 5-FU, Oxaliplatin, and Irinotecan (in any combination).
• Age ≥18 years
• ECOG performance status ≤ 1
• Life expectancy of greater than 3 months.
• Participants must meet the following organ and marrow function as defined below:
• Absolute Neutrophil Count (ANC) ≥ 1500 /mcL
• White Blood Cells (WBC) ≥ 2000 /mcL
• Platelets (PLT) ≥ 100,000 /mcL
• Hemoglobin (HGB) ≥ 8 g/dL without transfusion within 2 weeks of measurement
• AST and ALT ≤ 2.5 x ULN
• Total Bilirubin ≤ 1.5 x ULN OR \< 3 mg/dL for participants with Gilbert Syndrome
• Creatinine Clearance ≥ 40 mL/min if calculated using Cockcroft-Gault formula

You may not qualify if:

• Participants who have had chemotherapy, targeted small molecule therapy or study therapy within 14 days prior to starting protocol treatment, or those who have not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to agents administered more than 2 weeks earlier.
• EXCEPTION: Participants with ≤ Grade 2 neuropathy are permitted.
• If participant received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting protocol treatment.
• Known or suspected, active, autoimmune disease
• Condition requiring systemic treatment with either corticosteroids (\> 10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days prior to study drug administration.
• EXCEPTIONS: Inhaled or topical steroids and adrenal replacement doses \> 10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease. Subjects are permitted to use topical, ocular, intra-articular, intranasal, and inhalational corticosteroids (with minimal systemic absorption). Physiologic replacement doses of systemic corticosteroids are permitted, even if \>10 mg/day prednisone equivalents. A brief course of corticosteroids for prophylaxis (e.g., contrast dye allergy) or for treatment of non-autoimmune conditions (e.g., delayed-type hypersensitivity reaction caused by contact allergen) is permitted.
• Positive TB (Bacillus Tuberculosis) at screening. NOTE: skin test is not allowed. Interferon-Gamma Release Assay (IGRA)-based tests such as QuantiFERON TB Gold and T-Spot TB tests are acceptable.
• Partial or complete bowel obstruction within the last 3 months, signs/ symptoms of bowel obstruction, or known radiologic evidence of impeding obstruction.
• Refractory ascites defined as requiring 2 or more therapeutic paracenteses within the last 4 weeks, or ≥ times within the last 90 days, or ≥ time within the last 2 weeks prior to study entry, or requiring diuretics within 2 weeks of study entry.
• Known history of active or chronic HBV or HCV infection
• Known history of testing positive for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS). These participants are at increased risk of lethal infections when treated with marrow-suppressive therapy.
• \-- EXCEPTIONS: Patients with CD4 \>200 cells/mm3 and/or undetectable viral load are eligible.
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
• Known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
• Participant is pregnant, breastfeeding, expecting to conceive, or father children within the projected duration of the trial, starting with the consent visit through 120 days for woman and 120 days for men, after the last dose of study treatment.

Sponsors & Collaborators

• Massachusetts General Hospital: lead
• Agenus Inc.: collaborator

Study Sites (1)

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

Radiosurgery; balstilimab

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Radiotherapy; Therapeutics; Stereotaxic Techniques; Neurosurgical Procedures; Surgical Procedures, Operative; Investigative Techniques

Study Officials

• Aparna R. Parikh, MD

  Massachusetts General Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Aparna R. Parikh, MD

CONTACT

617-724-4000; aparna.parikh@mgh.harvard.edu

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: August 13, 2025
• First Posted: August 18, 2025
• Study Start (Estimated): June 1, 2026
• Primary Completion (Estimated): January 1, 2027
• Study Completion (Estimated): September 1, 2027
• Last Updated: April 9, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Data can be shared no earlier than 1 year following the date of publication
• Access Criteria: Contact the Partners Innovations team at http://www.partners.org/innovation

Locations

US (1)