Neoadjuvant Botensilimab and Balstilimab for the Treatment of Advanced Resectable Colorectal Cancer

NCT07595874 | Not Yet Recruiting Phase 2 FDA Drug

• 3 other identifiers: 25964NCI-2026-02923P30CA033572
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 11

Brief Summary

This phase II trial tests how well giving botensilimab and balstilimab prior or to surgery (neoadjuvent) works for the treatment of colorectal cancer that may have spread from where it first started to nearby tissue, lymph nodes, or distant parts of the body (advanced) and that can be removed by surgery (resectable) colorectal cancer. Immunotherapy with monoclonal antibodies, such as botensilimab and balstilimab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving botensilimab and balstilimab before surgery may make the tumor smaller. Giving neoadjuvant botensilimab and balstilimab may be effective for the treatment of advanced resectable colorectal cancer.

Conditions

Advanced Colon Adenocarcinoma; Advanced Colorectal Adenocarcinoma; Advanced Rectal Adenocarcinoma; Stage IIB Colon Cancer AJCC v8; Stage IIB Rectal Cancer AJCC v8; Stage IIC Colon Cancer AJCC v8; Stage IIC Rectal Cancer AJCC v8; Stage IIIA Colon Cancer AJCC v8; Stage IIIA Rectal Cancer AJCC v8; Stage IIIB Colon Cancer AJCC v8; Stage IIIB Rectal Cancer AJCC v8; Stage IIIC Colon Cancer AJCC v8; Stage IIIC Rectal Cancer AJCC v8

Outcome Measures

Primary Outcomes (1)

• Two-year disease-free survival rate

  Defined as the percentage of patients that remain free from any signs of colon cancer at two years post-enrollment. Will be compared to the historical control rate of 76.8% (from the FoXTROT adjuvant chemotherapy arm) using a one-sided, one-sample log-rank test.

  At 2 years post enrollment

Secondary Outcomes (9)

• Major pathologic response rate

  Up to 3 years

• Incidence of adverse events

  Up to 3 years

• Pathologic response rate

  Up to 3 years

• Three-year disease-free survival rate

  At 3 years post-enrollment

• Recurrence free survival

  Time from surgery to date of first cancer recurrence or death as a result of any cause, whichever occurs first, up to 3 years

Study Arms (1)

Treatment (botensilimab and balstilimab)

EXPERIMENTAL

Patients receive botensilimab IV, over 30 minutes, on day 1 and balstilimab IV, over 30 minutes, on days 1, 15, 29 and 43 in the absence of disease progression or unacceptable toxicity. 5-16 weeks later, patients then undergo standard of care resection surgery. Patients undergo CT scan and/or MRI and blood sample collection throughout the study.

Biological: Balstilimab; Procedure: Biospecimen Collection; Biological: Botensilimab; Procedure: Computed Tomography; Procedure: Magnetic Resonance Imaging

Interventions

Balstilimab BIOLOGICAL

Given IV

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

Treatment (botensilimab and balstilimab)

Biospecimen Collection PROCEDURE

Undergo blood sample collection

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

Treatment (botensilimab and balstilimab)

Botensilimab BIOLOGICAL

Given IV

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

Treatment (botensilimab and balstilimab)

Computed Tomography PROCEDURE

Undergo CT scan

Also known as: CAT, CAT Scan, Computed Axial Tomography, Computerized Axial Tomography, Computerized axial tomography (procedure), Computerized Tomography, Computerized Tomography (CT) scan, CT, CT Scan, Diagnostic CAT Scan, Diagnostic CAT Scan Service Type, tomography

Treatment (botensilimab and balstilimab)

Magnetic Resonance Imaging PROCEDURE

Undergo MRI

Also known as: Magnetic Resonance, Magnetic Resonance Imaging (MRI), Magnetic resonance imaging (procedure), Magnetic Resonance Imaging Scan, Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance, MR, MR Imaging, MRI, MRI Scan, MRIs, NMR Imaging, NMRI, Nuclear Magnetic Resonance Imaging, sMRI, Structural MRI

Treatment (botensilimab and balstilimab)

Eligibility Criteria

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

You may qualify if:

• Documented informed consent of the participant and Legally Authorized Representative (when applicable)
• Assent, when appropriate, will be obtained and documented for adults lacking capacity per institutional guidelines
• Agreement to allow the use of tissue from past and future surgery and standard of care biopsies
• Age: ≥ 18 years
• Eastern Cooperative Oncology Group (ECOG) ≤ 2
• Histologically confirmed or cytologically confirmed colorectal adenocarcinoma. Patients with high grade dysplasia on histology plus unequivocal endoscopic or radiological evidence of invasive cancer are eligible.
• Patients diagnosed with rectal cancer who will be treated like colon cancer with curative-intent surgery first and no radiation are also eligible, including:
• Upper rectum or rectosigmoid considered as non-rectal and not undergoing neoadjuvant treatment
• The tumor component should not extend to less 12 cm from the anal verge.
• Any patient with rectal cancer for whom radiotherapy is not advised is included in this protocol (i.e., excluding rectal adenocarcinomas warranting treatment with chemoradiation)
• Microsatellite stability by mismatch repair by immunohistochemistry, polymerase chain reaction and/or other Clinical Laboratory Improvement Amendments (CLIA) certified next generation sequencing. Only patients with mismatch repair proficient or microsatellite stable (pMMR/MSS) tumors are allowed to enroll in the study
• Candidate for and planning a curative resection. Must have surgeon identified
• T4, N+ (American Joint Committee on Cancer \[AJCC\] TNM staging criteria), or both by central radiographic assessment.
• Note: Patients with T3N0 stage IIA are excluded. Stage IIB, IIC, IIIA, IIIB, and IIIC are included. Patients with stage IV disease are excluded
• Absolute neutrophil count (ANC) ≥ 1,500/mm\^3

You may not qualify if:

• Any treatment for colorectal cancer prior to enrollment that includes (but not limited to) chemotherapy, surgery, radiation, immunotherapy and/or biological therapy.
• Note: Surgical intervention e.g. a diverting ostomy to relieve an obstruction from colorectal cancer, those patients will be allowed to enter the study as long as no distant metastatic disease
• Patients with a condition requiring systemic treatment with either corticosteroids (\> 10 mg daily prednisone equivalent) within 14 days or another immunosuppressive medication within 30 days of the first dose of study treatment. Inhaled or topical steroids, and adrenal replacement steroid doses \> 10 mg daily prednisone equivalent, are permitted in the absence of active autoimmune disease
• Prior allogeneic organ transplantation
• Herbal medications that require a prescription or are anti-cancer
• Other active malignancy. Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial. Please note: patients with more than 1 colorectal cancer tumor at diagnosis (as long as no stage IV disease) are allowed to participate. Pathologic response to each of the tumors will be examined
• Active acute colonic obstruction. Patients whose obstruction is relieved by a successful defunctioning stoma are allowed once recovered to a fitness level consistent with the other eligibility criteria
• Clinically significant uncontrolled illness
• Females only: Pregnant or breastfeeding
• Prior allergic reaction or hypersensitivity to any of the study drug components
• Active autoimmune disease or history of autoimmune disease that required systemic treatment within 2 years before starting treatment, i.e., with use of disease-modifying agents or immunosuppressive drugs (excluding hypothyroidism, vitiligo, and psoriasis that is controlled with topical management)
• History or current evidence of any condition, co-morbidity, therapy, that might confound the results of the study, interfere with the patient's participation for the full duration of the study, or is not in the best interest of the patient to participate, in the opinion of the treating Investigator
• Uncontrolled infection with human Immunodeficiency virus (HIV). Patients on stable highly active antiretroviral therapy (HAART) are eligible. Serological testing for HIV at screening is not required
• Uncontrolled infection with hepatitis B virus. Patients who are receiving or who have received anti-HBV therapy are eligible. Serological testing for HBV at screening is not required
• Known active hepatitis C virus (HCV) as determined by positive serology and confirmed by polymerase chain reaction (PCR). Patients on or who have received antiretroviral therapy are eligible. Serological testing for HCV at screening is not required

Sponsors & Collaborators

• City of Hope Medical Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (11)

CTCA at Western Regional Medical Center

Goodyear, Arizona, 85338, United States

Location

City of Hope Corona

Corona, California, 92882, United States

Location

City of Hope Medical Center

Duarte, California, 91010, United States

Location

City of Hope Seacliff

Huntington Beach, California, 92648, United States

Location

City of Hope at Irvine Lennar

Irvine, California, 92618, United States

Location

City of Hope at Long Beach Elm

Long Beach, California, 90813, United States

Location

City of Hope South Pasadena

South Pasadena, California, 91030, United States

Location

City of Hope Upland

Upland, California, 91786, United States

Location

City of Hope Atlanta Cancer Center

Newnan, Georgia, 30265, United States

Location

City of Hope at Illinois Chicago Downtown

Chicago, Illinois, 60611, United States

Location

City of Hope at Chicago

Zion, Illinois, 60099, United States

Location

MeSH Terms

Conditions

Colonic Neoplasms; Rectal Neoplasms

Interventions

balstilimab; Specimen Handling; Magnetic Resonance Spectroscopy

Condition Hierarchy (Ancestors)

Colorectal Neoplasms; 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)

Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Investigative Techniques; Spectrum Analysis; Chemistry Techniques, Analytical

Study Officials

• Pashtoon M Kasi

  City of Hope Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: May 5, 2026
• First Posted: May 19, 2026
• Study Start (Estimated): December 27, 2026
• Primary Completion (Estimated): May 27, 2027
• Study Completion (Estimated): May 27, 2027
• Last Updated: May 19, 2026

Record last verified: 2026-05

Locations

US (11)