Botensilimab, Balstilimab and Regorafenib for the Treatment of Patients With Microsatellite Stable Metastatic Colorectal Cancer Who Have Progressed on Prior Chemotherapy

NCT05672316 | Active Not Recruiting Phase 1 FDA Drug

• 3 other identifiers: 22351NCI-2022-10069P30CA033572
• Study Type: interventional
• Target: 28
• Locations: 1 country
• Sites: 1

Brief Summary

This phase I/II trial tests how well botensilimab, balstilimab, and regorafenib works in treating patients with microsatellite stable colorectal cancer that has spread from where it first started (primary site) to other places in the body (metastatic) or that may have spread from where it first started to nearby tissue, lymph nodes, or distant parts of the body (advanced) and who have progressed on prior chemotherapy. 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. Regorafenib binds to and inhibits growth factor receptors, which may inhibit the growth of new blood vessels that tumors need to grow. Giving botensilimab, balstilimab, and regorafenib in combination may work better in treating patients with metastatic colorectal cancer than giving these drugs alone.

Conditions

Advanced Colorectal Adenocarcinoma; Metastatic Colorectal Adenocarcinoma; Advanced Microsatellite Stable Colorectal Carcinoma; Metastatic Microsatellite Stable Colorectal Carcinoma; Stage III Colorectal Cancer AJCC v8; Stage IV Colorectal Cancer AJCC v8

Outcome Measures

Primary Outcomes (3)

• Recommended phase 2 dose of botensilimab, balstilimab, and regorafenib (Phase I)

  Will conduct a Simon 2-stage optimal design study.

  Cycle 1 (6 weeks)

• Incidence of dose limiting toxicities (DLT) (Phase I)

  Graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version (v) 5.0.

  Cycle 1 (6 weeks)

• Overall response rate (ORR) (Phase II)

  Assessed by Response Evaluation Criteria in Solid Tumors (RECIST) version (v) 1.1.

  Up to 2 years

Secondary Outcomes (8)

• Incidence of DLTs (Phase I)

  Up to 2 years

• ORR (Phase I)

  Up to 2 years

• Progression-free survival (PFS) (Phase I)

  Time to disease progression/ relapse or death as a result of any cause, assessed up to 2 years

• Overall survival (OS) (Phase I)

  Time to death as a result of any cause, assessed up to 2 years

• PFS (Phase II)

  Time to disease progression or death as a result of any cause, assessed up to 2 years

Study Arms (1)

Treatment (botensilimab, balstilimab and regorafenib)

EXPERIMENTAL

Patients receive botensilimab IV, balstilimab IV, and regorafenib PO on study. Patients also undergo CT and collection of blood throughout the study.

Biological: Balstilimab; Procedure: Biospecimen Collection; Biological: Botensilimab; Procedure: Computed Tomography; Drug: Regorafenib

Interventions

Botensilimab BIOLOGICAL

Given IV

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

Treatment (botensilimab, balstilimab and regorafenib)

Computed Tomography PROCEDURE

Undergo CT

Also known as: CAT, CAT Scan, Computed Axial Tomography, Computerized Axial Tomography, Computerized Tomography, CT, CT Scan, tomography

Treatment (botensilimab, balstilimab and regorafenib)

Regorafenib DRUG

Given PO

Also known as: BAY 73-4506, Regorafenib Anhydrous

Treatment (botensilimab, balstilimab and regorafenib)

Biospecimen Collection PROCEDURE

Undergo collection of blood

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

Treatment (botensilimab, balstilimab and regorafenib)

Balstilimab BIOLOGICAL

Given IV

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

Treatment (botensilimab, balstilimab and regorafenib)

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/or legally authorized representative.
• Assent, when appropriate, will be obtained per institutional guidelines
• Age: \>= 18 years
• Eastern Cooperative Oncology Group (ECOG) =\< 1
• Life expectancy \>= 3 months
• Able to swallow and absorb oral tablets
• Histological or cytological confirmed advanced, metastatic, or progressive proficient mismatch repair (pMMR)/MSS adenocarcinoma of colon or rectum
• Microsatellite status should be performed per local standard of practice (e.g., immunohistochemistry \[IHC\] and/or polymerase chain reaction \[PCR\], or next-generation sequencing). Only participants with pMMR/MSS mCRC are eligible
• Patients should have measurable metastatic disease as per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 guidelines
• Known extended RAS and BRAF status as per local standard of practice. TMB and PD-L1 status will be collected when available but not mandated for enrollment
• Patients must have progressed following exposure to all of the following agents:
• Fluoropyrimidines (capecitabine or 5-FU)
• Irinotecan
• Oxaliplatin
• Anti-EGFR therapy if RAS and BRAF wild type with left colon primary

You may not qualify if:

• Prior immunotherapy with PD-1 or PD-L1 or CTLA-4 targeting agents
• 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
• Surgical intervention within 4 weeks prior to study treatment, except for minor procedures such as port placement
• 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
• Uncontrolled hypertension, defined as systolic blood pressure (SBP) \> 150, diastolic blood pressure (DBP) \> 90
• History of acute thrombotic venous events in the last 30 days before enrollment. If within 30 days, the patient should be on anticoagulants and without symptoms
• Clinically significant (i.e., active) cardiovascular disease: cerebral vascular accident/stroke or myocardial infarction within 12 months of enrollment, unstable angina, congestive heart failure (New York Heart Association class \>= III), or serious uncontrolled cardiac arrhythmia requiring medication
• Obstructive bowel symptoms related to unresected primary or carcinomatosis
• Any persistent toxicities (Common Terminology Criteria for Adverse Events \[CTCAE\] grade \>= 2) from prior cancer therapy, excluding endocrinopathies stable on medication, stable neuropathy that is grade 1 or less, and alopecia
• Non-healing wounds
• Symptomatic active bleeding
• Active brain metastases or leptomeningeal metastases with the following exceptions:
• Treated brain metastases require a) surgical resection, or b) stereotactic radiosurgery. These patients must be off steroids \>= 10 days prior to randomization for the purpose of managing their brain metastases. Repeat brain imaging following surgical resection or stereotactic radiosurgery at least 4 weeks from treatment should document lack of progression

Sponsors & Collaborators

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

Study Sites (1)

City of Hope Medical Center

Duarte, California, 91010, United States

Location

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

balstilimab; Specimen Handling; regorafenib

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)

Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Investigative Techniques

Study Officials

• Marwan G Fakih

  City of Hope Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 3, 2023
• First Posted: January 5, 2023
• Study Start: May 11, 2023
• Primary Completion: May 10, 2025
• Study Completion (Estimated): August 25, 2026
• Last Updated: January 28, 2026

Record last verified: 2026-01

Locations

US (1)