Combination Immunotherapy in Colorectal Cancer

NCT05571293 | Suspended Phase 2 DMC FDA Drug

• 1 other identifier: 22-09025238
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 3

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.

Conditions

Colorectal Neoplasms

Keywords

Immunotherapy; Colorectal Cancer; PD-1; CTLA-4

Outcome Measures

Primary Outcomes (4)

• Cohort A and B: Pathological overall response (pOR) rate determined by analysis of tissue resected during surgery reported by cohort

  Resected tumors will be examined in their entirety, and regression of resected tumors was assessed by estimating the percentage of residual viable tumor of the macroscopically identifiable tumor bed, as identified on routine hematoxylin and eosin (H\&E) staining. In addition, regression will be classified using the Mandard tumor regression grading system. Major pathologic response (MPR) will be defined as ≤10% of residual viable tumor cells (or ≥ 90% response), corresponding to Mandard tumor regression grade 1 (CR) or 2 (near-CR). PR will be defined as at least 50% tumor regression. However, considering the lack of consensus on the definition of PR after immunotherapy, tumors with \>50% and \<90% residual viable tumor will be labeled accordingly as '10-50% tumor regression', as per the NICHE study (Chalabi et. al., 2020). When analyzing pMMR responders versus pMMR nonresponders, this subgroup will be included in the group of nonresponders.

  1-6 weeks following the second dose of balstilimab

• Cohort A: Number of participants who experience potentially treatment-related SAEs according to the Common Terminology Criteria for Adverse Events (CTCAE) v5.0 at 90 days following the last treatment with balstilimab or botensilimab

  Safety will be assessed by evaluation of the number of SAEs according to the Common Terminology Criteria for Adverse Events (CTCAE) v5.0 at 90 days post-the last dose of study drug

  90 days post-the last dose of study drug

• Cohort A: Number of participants who experience treatment-related complications leading to delays of 12 weeks or more in surgery after treatment initiation (Day 0)

  Any AEs or SAEs that lead to a delay in surgery greater than 12 weeks from treatment initiation (Day 0) will be recorded. If there are ≥ 2 patients out of the first 6 patients, or ≥ 4 patients out of the full 12 participants (≥33%), with AEs/SAEs that lead to a delay in surgery beyond 12 weeks from treatment initiation, with the exception of COVID-related procedural delays, then this combination of botensilimab and balstilimab, at these dosages will not be considered feasible in this population.

  Approximately Day 90

• Cohort C: Composite rate of clinical complete response or major pathological response at 6 months

  The joint patient-surgeon decision to defer surgery for a watch and wait (Watch-\&-Wait W\&W) approach is allowed as long as the patient is demonstrating sustained response as determined by clinical, radiographic, endoscopic, and/or blood-based biomarkers. For participants who elect to undergo surgery, pathological response will be determined as described above. The key endpoint here will be "Major pathological response (MPR; CR + near-CR). Patients who opt for non-operative management based on clinical response will be considered to have CR. Complete response will be determined by the treating physician and surgeon based on composite subjective and objective assessments of clinical, radiographic, endoscopic, blood-based biomarker assessments, and/or the absence of clinical and radiographic progression.

  6 months

Secondary Outcomes (1)

• All Cohorts: Changes in Minimal Residual Disease assessed using ctDNA pre- and 30 days post-surgical resection

  Baseline; 30 days post-surgical resection

Study Arms (3)

Cohort A: Botensilimab and balstilimab (bot/bal)

EXPERIMENTAL

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.

Drug: Botensilimab; Drug: Balstilimab

Cohort B:

EXPERIMENTAL

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.

Drug: Botensilimab; Drug: Balstilimab

Cohort C:

EXPERIMENTAL

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.

Drug: Botensilimab; Drug: Balstilimab

Interventions

Botensilimab DRUG

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

Cohort A: Botensilimab and balstilimab (bot/bal); Cohort B:; Cohort C:

Balstilimab DRUG

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

Cohort A: Botensilimab and balstilimab (bot/bal); Cohort B:; Cohort C:

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Weill Medical College of Cornell University: lead
• Agenus Inc.: collaborator

Study Sites (3)

Weill Cornell Medicine/New York-Presbyterian Brooklyn Methodist Hospital

Brooklyn, New York, 11215, United States

Location

Weill Cornell Medicine/NewYork Presbyterian - Queens

Flushing, New York, 11355, United States

Location

Weill Cornell Medicine/NewYork-Presbyterian Hospital

New York, New York, 10021, United States

Location

MeSH Terms

Conditions

Colorectal Neoplasms; Diabetes Mellitus, Insulin-Dependent, 12

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

• Manish Shah, M.D.

  Weill Medical College of Cornell University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 4, 2022
• First Posted: October 7, 2022
• Study Start: March 17, 2023
• Primary Completion: November 1, 2025
• Study Completion (Estimated): June 1, 2026
• Last Updated: July 30, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (3)