Combination Immunotherapy in Colorectal Cancer (NEST-1)

Weill Cornell Medicine (WCM)

Status and phase: Suspended; Phase 2

Conditions: Colorectal Neoplasms

Treatments: Drug: Balstilimab; Drug: Botensilimab

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT05571293

22-09025238

Details and patient eligibility

About

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.

Full 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.

Enrollment: 36 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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36 participants in 3 patient groups

Cohort A: Botensilimab and balstilimab (bot/bal)

Experimental group

Description:

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.

Treatment:

Drug: Balstilimab

Drug: Botensilimab

Cohort B:

Experimental group

Description:

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.

Treatment:

Drug: Balstilimab

Drug: Botensilimab

Cohort C:

Experimental group

Description:

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.

Treatment:

Drug: Balstilimab

Drug: Botensilimab