NCT05672316

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

A Phase I/II Trial of Botensilimab, Balstilimab and Regorafenib (BBR) in Patients With Microsatellite Stable (MSS) Metastatic Colorectal Cancer Who Progressed on Prior Chemotherapy

• Status: Active Not Recruiting
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 28 (actual)
• Sponsor: City of Hope Medical Center · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

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.

Detailed description

PRIMARY OBJECTIVES: I. To identify the recommended phase 2 dose (RP2D) of botensilimab, balstilimab, and regorafenib (BBR) in patients with chemotherapy-resistant microsatellite stable (MSS) metastatic colorectal cancer (MSS mCRC). (Phase I) II. To estimate the overall response rate (ORR) of botensilimab, balstilimab, and regorafenib in patients with chemotherapy-resistant MSS mCRC, with and without liver metastatic disease. (Phase II) SECONDARY OBJECTIVES: I. Describe the safety of botensilimab, balstilimab, and regorafenib at all evaluable dose levels. (Phase I) II. Describe the efficacy of BBR in terms of ORR, progression free survival (PFS) and overall survival (OS). (Phase I) III. To evaluate the safety/feasibility of botensilimab, balstilimab, and regorafenib through the assessment of adverse events. (Phase II) IV. Estimate the PFS, OS and duration of response (DOR). (Phase II) CORRELATIVE OBJECTIVES: I. Evaluate potential circulating biomarkers of response, resistance, activity, and toxicity. (Phase I/II) II. Correlate baseline molecular biomarkers (RAS, BRAF, TMB, and PD-L1 if available), with overall outcome. (Phase I/II) OUTLINE: This is a phase I, dose-escalation study of botensilimab followed by a phase II study. Patients receive botensilimab intravenously (IV), balstilimab IV, and regorafenib orally (PO) on study. Patients also undergo computed tomography (CT) and collection of blood throughout the study.

Conditions

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

Interventions

Type	Name	Description
BIOLOGICAL	Balstilimab	Given IV
PROCEDURE	Biospecimen Collection	Undergo collection of blood
BIOLOGICAL	Botensilimab	Given IV
PROCEDURE	Computed Tomography	Undergo CT
DRUG	Regorafenib	Given PO

Timeline

• Start date: 2023-05-11
• Primary completion: 2025-05-10
• Completion: 2026-08-25
• First posted: 2023-01-05
• Last updated: 2026-01-28

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study