Combination Immunotherapy in Colorectal Cancer

NCT ID: NCT05571293

Last Updated: 2025-07-30

Basic Information

• Recruitment Status: SUSPENDED
• Clinical Phase: PHASE2
• Total Enrollment: 36 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-03-17
• Study Completion Date: 2026-06-30

Brief Summary

This is a pilot study to see whether a combination of two investigational drugs that target the immune system can be given to people with colorectal cancer before surgically removing the tumor. This study is also being done to see what side effects this combination of drugs has and what effect they have on colorectal cancer. The two monoclonal antibodies are balstilimab, a programmed cell death protein 1 (PD-1) inhibitor, and botensilimab, a cytotoxic T lymphocyte-associated protein 4 (CTLA-4) inhibitor. This study has 3 cohorts. Participants in Cohort A will receive a total of 2 doses of balstilimab and a single dose of botensilimab, both given intravenously (IV), before surgery. Participants in Cohort B and C will receive a total of 4 doses of balstilimab and a single dose of botensilimab, both given intravenously (IV), before surgery. Participants in Cohort C must have dMMR/MSI-High colorectal cancer.

Detailed Description

This is a pilot study to assess the feasibility, safety, and efficacy of using a combination of a programmed cell death protein 1 (PD-1) inhibitor (balstilimab) and cytotoxic T lymphocyte-associated protein 4 (CTLA-4) inhibitor (botensilimab) in the neoadjuvant setting in patients with colorectal cancer, prior to resection. This is a single-center, open-label, pilot study in which patients will receive 2 or 4 doses of intravenous (IV) balstilimab (each dose approximately 2 weeks apart), and a single dose of botensilimab IV, prior to resection in patients with colon cancer. Following surgical resection, participants will return to the clinic for 1-2 post-op follow-up visits.

Conditions

Colorectal Neoplasms

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Cohort A: Botensilimab and balstilimab (bot/bal)

Botensilimab and balstilimab are both monoclonal antibodies that are administered intravenously. Two doses of balstilimab (240 mg IV), will be administered approximately 2 weeks apart. A single dose of botensilimab (75 mg IV) will be administered on the same day as the first dose of balstilimab. Surgical resection will occur 1-6 weeks following the second dose of balstilimab.

Group Type: EXPERIMENTAL

Botensilimab

Intervention Type: DRUG

Botensilimab, a CTLA-4 inhibitor, will be administered prior to surgical resection as described in the arm description.

Balstilimab

Intervention Type: DRUG

Balstilimab, a PD-1 inhibitor, will be administered prior to surgical resection as described in the arm description.

Cohort B:

Botensilimab and balstilimab are both monoclonal antibodies that are administered intravenously. Four doses of balstilimab (240 mg IV), will be administered approximately 2 weeks apart. A single dose of botensilimab (75 mg IV) will be administered on the same day as the first dose of balstilimab. Surgical resection will occur 1-6 weeks following the fourth dose of balstilimab.

Group Type: EXPERIMENTAL

Botensilimab

Intervention Type: DRUG

Botensilimab, a CTLA-4 inhibitor, will be administered prior to surgical resection as described in the arm description.

Balstilimab

Intervention Type: DRUG

Balstilimab, a PD-1 inhibitor, will be administered prior to surgical resection as described in the arm description.

Cohort C:

Botensilimab and balstilimab are both monoclonal antibodies that are administered intravenously. Four doses of balstilimab (240 mg IV), will be administered approximately 2 weeks apart. A single dose of botensilimab (75 mg IV) will be administered on the same day as the first dose of balstilimab. Surgical resection will occur 1-6 weeks following the fourth dose of balstilimab. Cohort C only includes patients with dMMR/MSI-High colorectal cancer.

Group Type: EXPERIMENTAL

Botensilimab

Intervention Type: DRUG

Botensilimab, a CTLA-4 inhibitor, will be administered prior to surgical resection as described in the arm description.

Balstilimab

Intervention Type: DRUG

Balstilimab, a PD-1 inhibitor, will be administered prior to surgical resection as described in the arm description.

Interventions

Botensilimab

Botensilimab, a CTLA-4 inhibitor, will be administered prior to surgical resection as described in the arm description.

Intervention Type: DRUG

Balstilimab

Balstilimab, a PD-1 inhibitor, will be administered prior to surgical resection as described in the arm description.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• 18 years of age or older
• Histologically, cytologically, or clinically confirmed adenocarcinoma of the colon or rectal cancer as long as there is no plans for neoadjuvant radiation for the patients with rectal cancer. Note: patients can enroll in cohort B while awaiting mismatch repair testing results. If noted to be dMMR/MSI-High, they would be still considered evaluable and moved to cohort C.
• If capable of becoming pregnant, or getting someone else pregnant, must be willing to use highly effective contraception from Screening period through 90 days following the last dose of study drug

Exclusion Criteria

• Metastatic cancer (cancer that has spread to other parts of the body)
• Previous treatment with immune checkpoint inhibitors targeting CTLA-4, PD-1 or PD-L1
• Currently participating in another study and receiving a study drug
• History of severe allergic reactions to immunotherapies
• Pregnant or breastfeeding
• Active infection requiring treatment
• On immunosuppressive medications
• Active cardiovascular disease, such as stroke or myocardial infarction within 6 months of enrollment, unstable angina, congestive heart failure, or serious uncontrolled cardiac arrhythmia requiring medication that may prevent surgery

Participants in Cohort C must be dMMR/MSI-High.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Agenus Inc.

INDUSTRY

Sponsor Role: collaborator

Weill Medical College of Cornell University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Manish Shah, M.D.

Role: PRINCIPAL_INVESTIGATOR

Weill Medical College of Cornell University

Locations

Weill Cornell Medicine/New York-Presbyterian Brooklyn Methodist Hospital

Brooklyn, New York, United States

Weill Cornell Medicine/NewYork Presbyterian - Queens

Flushing, New York, United States

Weill Cornell Medicine/NewYork-Presbyterian Hospital

New York, New York, United States

Countries

United States

Other Identifiers

22-09025238

Identifier Type: -

Identifier Source: org_study_id