Clinical trial NCT05571293: Combination Immunotherapy in Colorectal Cancer
Official title: Novel Exploratory Study to Test Combination of Botensilimab and Balstilimab Immunotherapy in Resectable Colorectal Cancer Patients
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Colorectal Neoplasms
Keywords: Immunotherapy
Colorectal Cancer
PD-1
CTLA-4
Lead sponsor: Weill Medical College of Cornell University
Sponsor class: OTHER
Collaborators: name: Agenus Inc.
First posted: 2022-10-07
Enrollment: 36
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Cohort A and B: Pathological overall response (pOR) rate determined by analysis of tissue resected during surgery reported by cohort
timeFrame: 1-6 weeks following the second dose of balstilimab
measure: 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
timeFrame: 90 days post-the last dose of study drug
measure: 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)
timeFrame: Approximately Day 90
measure: Cohort C: Composite rate of clinical complete response or major pathological response at 6 months
timeFrame: 6 months
Secondary outcomes:
measure: All Cohorts: Changes in Minimal Residual Disease assessed using ctDNA pre- and 30 days post-surgical resection
timeFrame: Baseline; 30 days post-surgical resection
Other outcomes:
Locations:
city: Brooklyn
country: United States
facility: Weill Cornell Medicine/New York-Presbyterian Brooklyn Methodist Hospital
state: New York
city: Flushing
country: United States
facility: Weill Cornell Medicine/NewYork Presbyterian - Queens
state: New York
city: New York
country: United States
facility: Weill Cornell Medicine/NewYork-Presbyterian Hospital
state: New York
Study officials:
affiliation: Weill Medical College of Cornell University
name: Manish Shah, M.D.
role: PRINCIPAL_INVESTIGATOR
References: