Botensilimab + Balstilimab vs Best Supportive Care as Therapy in Chemo-refractory, Unresectable, Colorectal Adenocarcinoma

NCT07152821 | Terminated Phase 3 DMC FDA Drug

• 1 other identifier: CO33
• Study Type: interventional
• Target: 21
• Locations: 1 country
• Sites: 1

Brief Summary

This study is being done to answer the main question of: Do patients with colorectal cancer that cannot be removed by surgery, that is treated with two new immunotherapy drugs, botensilimab and balstilimab, live longer? Other important questions include: Is their quality of life better? Do their tumours slow in growth or possibly shrink in size? Are there markers in their tumour or blood that can predict whether they achieve any of these benefits? In addition, the study is done to confirm the safety of these immunotherapy drugs and to determine how long it takes for the body to metabolize them.

Conditions

Colorectal Cancer

Outcome Measures

Primary Outcomes (1)

• Overall Survival

  34 months

Secondary Outcomes (8)

• Progression Free Survival (PFS) based on RECIST 1.1 criteria

  34 months

• Overall Response Rate (ORR) based on RECIST 1.1 criteria

  34 months

• Clinical Benefit Rate (CBR) at 6 months based on RECIST 1.1 criteria

  34 months

• Health Related Quality of Life (HRQoL) utilizing EORTC QLQ-C30

  34 months

• Health Related Quality of Life (HRQoL) utilizing EORTC QLQ-CR29

  34 months

Study Arms (2)

Best Supportive Care

ACTIVE COMPARATOR

Other: Best Supportive Care

Botensilimab + Balstilimab and Best Supportive Care

EXPERIMENTAL

Other: Best Supportive Care; Drug: Balstilimab; Drug: Botensilimab

Interventions

Balstilimab DRUG

450mg IV every 3 weeks

Botensilimab + Balstilimab and Best Supportive Care

Botensilimab DRUG

75mg IV every 6 weeks x 4 doses

Botensilimab + Balstilimab and Best Supportive Care

Best Supportive Care OTHER

Measures designed to provide palliation of symptoms and improve quality of life as much as possible

Best Supportive Care; Botensilimab + Balstilimab and Best Supportive Care

Eligibility Criteria

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

You may qualify if:

• Must have histologically confirmed colorectal adenocarcinoma that is not deficient mismatch repair (dMMR) or microsatellite instability-high (MSI-H).
• Received and failed all prior available therapies, such that the standard of care for the patient would be best supportive care (BSC).
• Must have an Eastern Cooperative Oncology Group (ECOG) performance status 0, or 1.
• Must have presence of measurable or evaluable disease as defined by Response Evaluation Criteria in Solid Tumours (RECIST 1.1).
• A life expectancy of ≥ 12 weeks at the time of study entry.
• Must be ≥ 18 years of age.
• Participants must consent to provision of, and investigator must agree to submit, a representative archival formalin fixed paraffin block of tumour tissue for correlative analyses when tumour tissue is available.
• Participants must have adequate organ and marrow function measured within 14 days prior to randomization.
• Participant is able (i.e. sufficiently fluent) and willing to complete the quality of life and health utility questionnaires in either English or French.
• Participant consent must be appropriately obtained in accordance with applicable local and national regulatory requirements.
• Participants must be accessible for treatment and follow-up. Investigators must assure themselves the participants enrolled on this trial will be available for complete documentation of the treatment, adverse events, and follow-up.
• In accordance with CCTG policy, protocol treatment is to begin within 2 working days of participant enrolment.
• Participants of childbearing potential or partners of participants of childbearing potential must have agreed to use a highly effective contraceptive method

You may not qualify if:

• Participants with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen may be eligible for this trial, however, consultation with CCTG in advance of enrolment is required.
• A history of primary immunodeficiency, solid organ transplant or allogeneic bone marrow transplant.
• Current or prior use of immunosuppressive medication within 7 days before the first dose of study drugs, with the exceptions of intranasal and inhaled corticosteroids or systemic corticosteroids at physiological doses, which are not to exceed 10 mg/day of prednisone, or an equivalent corticosteroid.
• Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease that has required systemic treatment within 2 years of the start of study drug.
• Active or uncontrolled intercurrent illness.
• Active brain metastases or leptomeningeal metastases.
• Receipt of live attenuated vaccination administered within 30 days prior to randomization.
• Lactating women who choose to breast feed.
• Any active disease condition which would render the protocol treatment dangerous or impair the ability of the participant to receive protocol therapy.
• Any condition that does not permit compliance with the protocol.
• Receipt of anti-cancer chemotherapy or biologic therapy within the lesser of i) 21 days, or ii) the usual cycle length of the regimen prior to the first planned dose of study drug.
• Receipt of radiotherapy or investigational agents within four weeks of first planned dose of study drug.
• Any unresolved toxicity (≥ CTCAE grade 2) from previous anti-cancer therapy.
• Known allergy or hypersensitivity to any of the study drugs or any of the study drug excipients.
• History of partial or complete bowel obstruction within the last 3 months prior to study enrolment, signs/symptoms of bowel obstruction or known radiologic evidence of impending obstruction.

Sponsors & Collaborators

• Agenus Inc.: collaborator
• Canadian Cancer Trials Group: lead
• UNICANCER: collaborator
• Australasian Gastro-Intestinal Trials Group: collaborator

Study Sites (1)

Kingston Health Science Centre

Kingston, Ontario, K0H1H0, Canada

Location

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

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

Study Officials

• Jonathan Loree

  BCCA-Vancouver Cancer Centre

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 26, 2025
• First Posted: September 3, 2025
• Study Start: March 31, 2026
• Primary Completion: July 13, 2026
• Study Completion: July 13, 2026
• Last Updated: July 16, 2026

Record last verified: 2026-07

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1)