A Study of Botensilimab and Balstilimab for Colorectal Cancer With ctDNA+ After Surgery and Chemotherapy
Phase II Study of Adjuvant Botensilimab in Combination With Balstilimab in Patients With Colorectal Cancer and Persistent Circulating Tumor DNA Following Surgery and Chemotherapy
1 other identifier
interventional
284
1 country
7
Brief Summary
The researchers are doing this study to find out whether the combination of botensilimab and balstilimab (BOT/BAL), followed by balstilimab alone, is an effective treatment for people with microsatellite stable (MSS) colorectal cancer or colorectal liver metastases (CRLM) who have measurable residual disease (MRD) after standard treatment with surgery and chemotherapy or total neoadjuvant therapy (TNT).
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_2 colorectal-cancer
Started Nov 2025
Typical duration for phase_2 colorectal-cancer
7 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
Study Start
First participant enrolled
November 7, 2025
CompletedFirst Submitted
Initial submission to the registry
November 10, 2025
CompletedFirst Posted
Study publicly available on registry
November 13, 2025
CompletedPrimary Completion
Last participant's last visit for primary outcome
November 1, 2030
ExpectedStudy Completion
Last participant's last visit for all outcomes
November 1, 2030
February 6, 2026
February 1, 2026
5 years
November 10, 2025
February 4, 2026
Conditions
Keywords
Outcome Measures
Primary Outcomes (4)
Rate of ctDNA clearance (Cohort 1a)
The 6 months ctDNA clearance will be estimated using the binomial distribution along with exact 95% confidence intervals separately in each cohort.
6 months
Rate of ctDNA clearance (Cohort 1b)
The 6 months ctDNA clearance will be estimated using the binomial distribution along with exact 95% confidence intervals separately in each cohort.
6 months
Recurrence-free survival (RFS) (Cohort 2a)
1 year
Recurrence-free survival (RFS) (Cohort 2b)
1 year
Study Arms (4)
Cohort 1a: Stage III MSS Colorectal Cancer (Botensilimab and Balstilimab)
EXPERIMENTALAll patients will receive botensilimab IV on day 1 of the 42 day cycle for 4 doses, balstilimab IV on days 1, 15, and 29 of the 42 day cycle. Patient then continues balstilimab alone for an additional two cycles IV on days 1, 15, and 29 of the 42 day cycle.
Cohort 1b: MSS CRLM (Botensilimab and Balstilimab)
EXPERIMENTALAll patients will receive botensilimab IV on day 1 of the 42 day cycle for 4 doses, balstilimab IV on days 1, 15, and 29 of the 42 day cycle. Patient then continues balstilimab alone for an additional two cycles IV on days 1, 15, and 29 of the 42 day cycle.
Cohort 2a: Stage 3 MSS Colorectal Cancer (Botensilimab and Balstilimab vs. Placebo) Randomized
EXPERIMENTALAll patients will receive botensilimab IV on day 1 of the 42 day cycle for 4 doses, balstilimab IV on days 1, 15, and 29 of the 42 day cycle. Patient then continues balstilimab alone for an additional two cycles IV on days 1, 15, and 29 of the 42 day cycle OR Placebo
Cohort 2b: MSS CRLM (Botensilimab and Balstilimab vs. Placebo) Randomized
EXPERIMENTALAll patients will receive botensilimab IV on day 1 of the 42 day cycle for 4 doses, balstilimab IV on days 1, 15, and 29 of the 42 day cycle. Patient then continues balstilimab alone for an additional two cycles IV on days 1, 15, and 29 of the 42 day cycle OR Placebo
Interventions
All patients will receive botensilimab IV on day 1 of the 42 day cycle for 4 doses
All patients will receive balstilimab IV on days 1, 15, and 29 of the 42 day cyclePatient then continues balstilimab alone for an additional two cycles IV on days 1, 15, and 29 of the 42 day cycle.
Placebo
Eligibility Criteria
You may qualify if:
- Subject or legally authorized representative, is willing and able to provide written informed consent.
- Histologically- or cytologically- confirmed colorectal cancer.
- ≥ 18 years of age on day of signing informed consent.
- Consent for use of archival tissue and blood draws for research purposes.
- Performance status of ECOG 0 or 1.
- Known non-MSI-H/pMMR by IHC, PCR or NGS testing. MSKCC confirmation of non-MSI-H/pMMR status is not mandatory prior to enrollment and treatment on the study. For patients with outside testing, if sufficient tissue is available testing may be repeated at MSKCC and will not impact initial eligibility.
- Consent to undergo MSK IMPACT or NGS, if not previously done
- Disease specific criteria:
- Cohorts 1a and 2a: Undergone a complete surgical resection (R0) for stage III colon or rectal cancer, followed by adjuvant chemotherapy with FOLFOX or CAPEOX. Post-operative chemotherapy not required if received previous oxaliplatin-based therapy. Total Neoadjuvant Therapy for rectal cancer with complete clinical and radiographic response is allowed.
- Cohorts 1b and 2b: Undergone a complete surgical resection (R0) for liver metastasis (ablation or stereotactic body radiation therapy \[SBRT\], but not Y-90, is permitted) and completed standard peri-operative chemotherapy. Peri-operative chemotherapy not required if received previous oxaliplatin-based therapy. Prior floxuridine via Hepatic Arterial Infusion Pump is permitted. Completed definitive treatment for the primary tumor including (R0) resection, or Total Neoadjuvant Therapy for rectal cancer with complete clinical and radiographic response.
- Positive ctDNA following completion of appropriate standard of care therapy.
- Patients must sign informed consent within 6 weeks of positive ctDNA result. The 6 weeks is considered from the date that the ctDNA is resulted, and not the date it is drawn.
- Adequate organ function, defined as:
- Absolute Neutrophil Count ≥ 1,500/mm3.
- Platelet count ≥ 75,000/mm3.
- +5 more criteria
You may not qualify if:
- Presence of metastatic or recurrent disease.
- Known DNA polymerase epsilon (POLE) or DNA polymerase delta (POLD) activating mutation.
- R1 (microscopic residual tumor) or R2 resection (macroscopic residual tumor at resection margin).
- Currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks of the first dose of treatment.
- Diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment.
- Patients who have received acute, low dose, systemic immunosuppressant medications (e.g., dexamethasone containing antiemetic regimen or steroids as CT scan contrast premedication) may be enrolled.
- The use of inhaled corticosteroids and mineralocorticoids (e.g., fludrocortisone) for patients with orthostatic hypotension or adrenocortical insufficiency is allowed.
- Hypersensitivity to botensilimab or balstilimab or any of its excipients.
- Chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to study Day 1 or who has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to a previously administered agent
- a. Note: If subject received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy.
- History of, or any evidence of active, non-infectious pneumonitis.
- Active infection requiring systemic therapy.
- Current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject's participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator.
- Known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
- Pregnant or breastfeeding or expecting to conceive or father children within the projected duration of the trial, starting with the pre-screening or screening visit through 90 days after the last dose of trial treatment.
- +9 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Memorial Sloan Kettering Cancer Centerlead
- Agenus Inc.collaborator
Study Sites (7)
Memorial Sloan Kettering Basking Ridge (Limited Protocol Activities)
Basking Ridge, New Jersey, 07920, United States
Memorial Sloan Kettering Monmouth (Limited Protocol Activities)
Middletown, New Jersey, 07748, United States
Memorial Sloan Kettering Bergen (Limited Protocol Activities)
Montvale, New Jersey, 07645, United States
Memorial Sloan Kettering Commack (Limited Protocol Activities)
Commack, New York, 11725, United States
Memorial Sloan Kettering Westchester (All Protocol Activities)
Harrison, New York, 10604, United States
Memorial Sloan Kettering Cancer Center (All Protocol Activities)
New York, New York, 10065, United States
Memorial Sloan Kettering Nassau (Limited Protocol Activities)
Rockville Centre, New York, 11553, United States
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Neil Segal, MD, PhD
Memorial Sloan Kettering Cancer Center
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- RANDOMIZED
- Masking
- DOUBLE
- Who Masked
- PARTICIPANT, INVESTIGATOR
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
November 10, 2025
First Posted
November 13, 2025
Study Start
November 7, 2025
Primary Completion (Estimated)
November 1, 2030
Study Completion (Estimated)
November 1, 2030
Last Updated
February 6, 2026
Record last verified: 2026-02
Data Sharing
- IPD Sharing
- Will share
Memorial Sloan Kettering Cancer Center supports the international committee of medical journal editors (ICMJE) and the ethical obligation of responsible sharing of data from clinical trials. The protocol summary, a statistical summary, and informed consent form will be made available on clinicaltrials.gov when required as a condition of Federal awards, other agreements supporting the research and/or as otherwise required. Requests for deidentified individual participant data can be made beginning 12 months after publication and for up to 36 months post publication. Deidentified individual participant data reported in the manuscript will be shared under the terms of a Data Use Agreement and may only be used for approved proposals. Requests may be made to: crdatashare@mskcc.org.