Actively Recruiting
Phase II Study of Botensilimab and Balstilimab as Adjuvant Treatment for Colorectal Cancer with Persistent Circulating Tumor DNA After Surgery and Chemotherapy
Led by Memorial Sloan Kettering Cancer Center · Updated on 2026-02-06
284
Participants Needed
7
Research Sites
N/A
Total Duration
On this page
Sponsors
M
Memorial Sloan Kettering Cancer Center
Lead Sponsor
A
Agenus Inc.
Collaborating Sponsor
AI-Summary
What this Trial Is About
Researchers are evaluating whether the combination of botensilimab and balstilimab (BOT/BAL), followed by balstilimab alone, can be an effective treatment for people with microsatellite stable (MSS) colorectal cancer or colorectal liver metastases (CRLM) who have measurable residual disease (MRD) after standard surgery and chemotherapy or total neoadjuvant therapy (TNT). This phase II study includes patients with persistent circulating tumor DNA (ctDNA) after treatment, aiming to understand treatment impact on disease recurrence. The study has two parts, each with two cohorts. Part 1 is a non-randomized study of 54 subjects assessing ctDNA clearance in patients with stage III non-MSI-H/pMMR colorectal cancer or MSS CRLM after surgery and chemotherapy. Part 2 is a randomized, placebo-controlled, double-blind study of 230 patients assessing recurrence-free survival (RFS). All patients receive botensilimab intravenously on day 1 of a 42-day cycle for 4 doses, and balstilimab intravenously on days 1, 15, and 29 of the same cycle. After these cycles, balstilimab alone continues for two more cycles on the same schedule. In Part 2, some patients may receive a placebo instead of balstilimab alone during the later cycles. Participants will be monitored through blood tests for ctDNA clearance and recurrence-free survival over 6 months to 1 year, depending on their cohort. The study includes assessments of disease status and safety monitoring during treatment cycles. Patients must consent to tissue and blood sample use for research and undergo genetic testing if not previously done. The total duration of participation varies by cohort and study part, with close follow-up for treatment effects and disease recurrence.
CONDITIONS
Brief Title
A Study of Botensilimab and Balstilimab for Colorectal Cancer With ctDNA+ After Surgery and Chemotherapy
Who Can Participate
Eligibility Criteria
You may qualify if you...
- Age 18 years or older at the time of informed consent
- Histologically- or cytologically-confirmed colorectal cancer
- Willing and able to provide written informed consent
- Consent for use of archival tissue and blood samples for research
- Performance status of ECOG 0 or 1
- Known non-MSI-H/pMMR status by testing
- For cohorts 1a and 2a: Complete surgical resection (R0) for stage III colon or rectal cancer followed by adjuvant chemotherapy or total neoadjuvant therapy
- For cohorts 1b and 2b: Complete surgical resection (R0) for liver metastasis with completed standard peri-operative chemotherapy
- Positive circulating tumor DNA (ctDNA) after completing standard care
- Signed informed consent within 6 weeks of positive ctDNA result
- Adequate organ function including specific blood counts and liver/kidney function
- Use of effective contraception during the study and for 5 months after last treatment (if of childbearing potential)
You will not qualify if you...
- Presence of metastatic or recurrent disease
- Known activating mutation in DNA polymerase epsilon (POLE) or delta (POLD)
- Incomplete surgical resection (R1 or R2)
- Participation in another investigational study within 4 weeks prior to treatment
- Immunodeficiency or systemic immunosuppressive therapy within 7 days before treatment
- Hypersensitivity to botensilimab, balstilimab, or their components
- Chemotherapy, targeted therapy, or radiation within 2 weeks prior to treatment start
- History or evidence of active non-infectious pneumonitis
- Active infection requiring systemic therapy
- Conditions or therapies that may interfere with trial participation
- Psychiatric or substance abuse disorders interfering with cooperation
- Pregnant, breastfeeding, or planning pregnancy during study and 90 days after last dose
- Prior therapy with anti-PD-1, anti-PD-L1, or anti-CTLA-4 agents
- Active or recent autoimmune disease requiring systemic treatment
- Known active tuberculosis or uncontrolled HIV infection
- Active hepatitis B or C infection
- Receipt of live vaccine within 30 days before study therapy start
AI-Screening
AI-Powered Screening
Complete this quick 3-step screening to check your eligibility
Your Study Journey
Duration - 2 to 4 weeks
Participants are screened for eligibility to participate in the trial.
Duration - Approximately 6 months (6 cycles of 42 days)
Participants receive botensilimab and balstilimab intravenously in cycles. Botensilimab is given on day 1 of each 42-day cycle for 4 doses. Balstilimab is given on days 1, 15, and 29 of each 42-day cycle for 6 doses total, with the last two cycles receiving balstilimab alone.
Multiple IV visits on days 1, 15, and 29 of each 42-day cycle for up to 6 cycles
Trial Site Locations
Total: 7 locations
1
Memorial Sloan Kettering Basking Ridge (Limited Protocol Activities)
Basking Ridge, New Jersey, United States, 07920
Actively Recruiting
2
Memorial Sloan Kettering Monmouth (Limited Protocol Activities)
Middletown, New Jersey, United States, 07748
Actively Recruiting
3
Memorial Sloan Kettering Bergen (Limited Protocol Activities)
Montvale, New Jersey, United States, 07645
Actively Recruiting
4
Memorial Sloan Kettering Commack (Limited Protocol Activities)
Commack, New York, United States, 11725
Actively Recruiting
5
Memorial Sloan Kettering Westchester (All Protocol Activities)
Harrison, New York, United States, 10604
Actively Recruiting
6
Memorial Sloan Kettering Cancer Center (All Protocol Activities)
New York, New York, United States, 10065
Actively Recruiting
7
Memorial Sloan Kettering Nassau (Limited Protocol Activities)
Rockville Centre, New York, United States, 11553
Actively Recruiting
Research Team
N
Neil Segal, MD, PhD
L
Luis Diaz, MD
How is the study designed?
Study Type
INTERVENTIONAL
Masking
DOUBLE
Allocation
RANDOMIZED
Model
PARALLEL
Primary Purpose
TREATMENT
Number of Arms
4
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