Testing the Combination of Anti-Cancer Drugs, Botensilimab (AGEN1181) and Balstilimab (AGEN2034), After Standard Treatment for Colorectal Cancer, Combat Trial

NCT07551596 | Not Yet Recruiting Phase 2 FDA Drug

• 3 other identifiers: NCI-2026-0278410741UM1CA186688
• Study Type: interventional
• Target: 20
• Locations: 0 countries
• Sites: N/A

Brief Summary

This phase II trial tests the effect of the botensilimab in combination with balstilimab in treating patients with stage II/III colorectal adenocarcinoma with detectable circulating tumor (ct) deoxyribonucleic acid (DNA) in the blood. Immunotherapy with monoclonal antibodies, such as botensilimab and balstilimab, may help the body's immune system attack the tumor, and may interfere with the ability of tumor cells to grow and spread. Giving botensilimab and balstilimab may be an effective combination to remove any remaining microscopic cancer cells in the bloodstream in patients with stage II/III colorectal adenocarcinoma. In addition, clearing the ctDNA from the blood may serve as an early indicator of treatment response.

Conditions

Colorectal Adenocarcinoma; Stage II Colorectal Cancer AJCC v8; Stage III Colorectal Cancer AJCC v8

Outcome Measures

Primary Outcomes (1)

• Circulating tumor deoxyribonucleic acid (ctDNA) clearance

  Will be defined as clearance of ctDNA and no radiographic evidence of disease. Will estimate clearance rate and its 95% confidence interval.

  Up to 6 months

Secondary Outcomes (5)

• ctDNA clearance rate

  At 3 months

• Recurrence-free survival (RFS)

  From the start of botensilimab (AGEN1181) and balstilimab (AGEN2034) to recurrence of tumor or death, whichever occurred first, assessed up to 3 years

• Overall survival (OS)

  From the first dose of study treatment to the date of death from any cause, assessed up to 3 years

• Incidence and severity of adverse events (AEs)

  Up to 90 days after last dose of study treatment

• Determination if Cancer Immunotherapy Response Classifier may predict benefit

  Up to 3 years

Other Outcomes (5)

• Time to ctDNA negative status

  At baseline, during and following treatment, assessed up to 3 years

• Duration of ctDNA negative status

  During and following treatment, assessed up to 3 years

• Overall ctDNA negative rate

  During and following treatment, assessed up to 3 years

Study Arms (1)

Treatment (balstilimab, botensilimab)

EXPERIMENTAL

Patients receive balstilimab IV over 30 minutes on days 1 and 22 of cycles 1-4 and botensilimab IV over 30 minutes on days 1 of cycles 1 and 2. Treatment repeats every 42 days for up to 4 cycles (6 months) in the absence of disease progression or unacceptable toxicity. Patients also undergo urine and blood sample collection and imaging throughout the study. Additionally, patients may undergo optional tumor tissue biopsy on study.

Biological: Balstilimab; Procedure: Biopsy Procedure; Procedure: Biospecimen Collection; Biological: Botensilimab; Procedure: Radiographic Examination

Interventions

Balstilimab BIOLOGICAL

Given IV

Also known as: AGEN 2034, AGEN-2034, AGEN2034

Treatment (balstilimab, botensilimab)

Biopsy Procedure PROCEDURE

Undergo tumor tissue biopsy

Also known as: Biopsy, BIOPSY_TYPE, Bx

Treatment (balstilimab, botensilimab)

Biospecimen Collection PROCEDURE

Undergo urine and blood sample collection

Also known as: Biological Sample Collection, Biospecimen Collected, Specimen Collection

Treatment (balstilimab, botensilimab)

Botensilimab BIOLOGICAL

Given IV

Also known as: AGEN 1181, AGEN-1181, AGEN1181, Anti-CTLA-4 Monoclonal Antibody AGEN1181

Treatment (balstilimab, botensilimab)

Radiographic Examination PROCEDURE

Undergo imaging

Also known as: Radiographic Exam, Radiography

Treatment (balstilimab, botensilimab)

Eligibility Criteria

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

You may qualify if:

• Age ≥ 18 years. Because no dosing or adverse event data are currently available on the use of botensilimab (AGEN1181) in combination with balstilimab (AGEN2034) in patients \< 18 years of age, children are excluded from this study
• Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 2 (or Karnofsky ≥ 60%)
• Absolute neutrophil count ≥ 1,000/mcL
• Platelets ≥ 100,000/mcL
• Total bilirubin ≤ 1.5 x the institutional upper limit of normal (ULN)
• Patients with documented Gilbert's syndrome may be included if total bilirubin is ≤ 3 x ULN
• Aspartate aminotransferase (AST)(serum glutamic oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT)(serum glutamic pyruvic transaminase \[SGPT\]) ≤ 3 x institutional ULN
• Creatinine clearance ≥ 40 mL/min
• Creatinine clearance (Clcr) can either be measured in a 24-hour urine collection or estimated by the Cockcroft-Gault equation
• Histological confirmation of colorectal cancer (adenocarcinoma) (CRC)
• Post-R0 resection of stages II and III CRC and all planned adjuvant therapies have been completed
• No evidence of radiographic disease within 28 days (before or after) of a positive ctDNA assay
• Evident MRD as defined by positive ctDNA (Signatera MRD) assay. MRD status will be confirmed with the Signatera™ assay prior to initiation of therapy. The MRD status should be assessed at least 4 weeks post-surgery and at least 3 weeks after last chemo to avoid transient false positives. The window from MRD positivity to first dose should be no more than 90 days
• Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial
• For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated

You may not qualify if:

• Patients who are receiving any other investigational agents
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to botensilimab (AGEN1181) and balstilimab (AGEN2034)
• Patients that are pregnant, breast feeding, or planning to become pregnant while enrolled in the study, up to the end of treatment (EOT) visit, are excluded from this study because botensilimab (AGEN1181) and balstilimab (AGEN2034) are agents with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with botensilimab (AGEN1181) and balstilimab (AGEN2034), breastfeeding should be discontinued if the mother is treated with botensilimab (AGEN1181) and balstilimab (AGEN2034)
• Patients with microsatellite instability (MSI-high) or deficient mismatch repair (dMMR) CRC (MMR/MSI testing is required prior to enrollment)
• Concurrent treatment with a drug with which the interactions are considered clinically significant by the investigator. Major surgical procedure or significant traumatic injury within 21 days before start of study medication \* Note: If participants received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy
• Systemic therapy with immunosuppressive agents within 7 days or use of any investigational drug within 28 days before the start of trial treatment
• Prior exposure to any immune checkpoint blockade agent or any other immunomodulatory agent used for antineoplastic therapy for metastatic (m)CRC
• Receipt of any organ transplantation, including allogeneic stem cell transplantation (exception: transplants that do not require immunosuppression, such as hair transplant)
• Patients with active autoimmune disease that might deteriorate when receiving an immunostimulatory agent
• Patients with known severe hypersensitivity reactions to monoclonal antibodies (grade ≥ 3 National Cancer Institute \[NCI\]-Common Terminology Criteria for Adverse Events \[CTCAE\] version \[v\] 5.0), any history of anaphylaxis, or recent (within 5 months) history of uncontrolled asthma
• Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trial, patients should be class II or better
• Patients with clinically relevant diseases (for example, inflammatory bowel disease) and / or uncontrolled medical conditions, which, in the opinion of the Investigator, might impair the subject's tolerance or ability to participate in the trial. Stable, well-controlled conditions such as vitiligo, type 1 diabetes, or hypothyroidism on replacement can be allowed
• Failure to recover from any other toxicity (other than immune-related toxicity) related to previous anticancer treatment to ≤ grade 2
• Receipt of a live-virus vaccine within 30 days prior to first dose of study drug (seasonal flu vaccines that do not contain live virus are permitted)
• Evidence of any serious bacterial, viral, parasitic, or systemic fungal infections within the 30 days prior to the first dose of study drug

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

balstilimab; Biopsy; Specimen Handling; X-Rays

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

Intervention Hierarchy (Ancestors)

Cytodiagnosis; Cytological Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Diagnostic Techniques, Surgical; Surgical Procedures, Operative; Investigative Techniques; Electromagnetic Radiation; Electromagnetic Phenomena; Magnetic Phenomena; Physical Phenomena; Radiation; Radiation, Ionizing

Study Officials

• Kanwal P Raghav

  University of Texas MD Anderson Cancer Center LAO

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 24, 2026
• First Posted: April 27, 2026
• Study Start (Estimated): May 28, 2026
• Primary Completion (Estimated): September 30, 2026
• Study Completion (Estimated): September 30, 2026
• Last Updated: May 5, 2026

Record last verified: 2026-05

Data Sharing

• IPD Sharing: Will share