Botensilimab, Balstilimab and Regorafenib or Botensilimab and Balstilimab for the Treatment of Advanced or Metastatic Microsatellite Stable Colorectal Cancer
NCT Number: NCT06575725
Status: NOT_YET_RECRUITING
Study Type: INTERVENTIONAL
Phases: PHASE2
Conditions: Advanced Colon Adenocarcinoma|Advanced Colorectal Adenocarcinoma|Advanced Rectal Adenocarcinoma|Metastatic Colon Adenocarcinoma|Metastatic Colorectal Adenocarcinoma|Metastatic Rectal Adenocarcinoma|Stage III Colon Cancer AJCC v8|Stage III Colorectal Cancer AJCC v8|Stage III Rectal Cancer AJCC v8|Stage IV Colon Cancer AJCC v8|Stage IV Colorectal Cancer AJCC v8|Stage IV Rectal Cancer AJCC v8
Interventions: BIOLOGICAL: Balstilimab|PROCEDURE: Biopsy|PROCEDURE: Biospecimen Collection|BIOLOGICAL: Botensilimab|PROCEDURE: Computed Tomography|PROCEDURE: Magnetic Resonance Imaging|DRUG: Regorafenib
Sponsor: City of Hope Medical Center
Collaborators: National Cancer Institute (NCI)
Sex: ALL
Age: ADULT, OLDER_ADULT
Enrollment: 84
Study Design: Allocation: RANDOMIZED|Intervention Model: PARALLEL|Masking: NONE|Primary Purpose: TREATMENT
Start Date: 2024-11-01
Completion Date: 2027-01-28
Locations: City of Hope Medical Center, Duarte, California, 91010, United States

Summary:
This phase II trial studies how well the combination of botensilimab, balstilimab and regorafenib works compared to botensilimab and balstilimab in treating patients with microsatellite stable colorectal cancer that may have spread from where it first started to nearby tissue, lymph nodes, or distant parts of the body (advanced) or that has spread from where it first started (primary site) to other places in the body (metastatic). 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 is in a class of medications called kinase inhibitors. It works by blocking the action of an abnormal protein that signals tumor cells to multiply. This helps to slow or stop the spread of tumor cells. The combination of botensilimab, balstilimab and regorafenib or botensilimab and balstilimab may be a safe and effective treatment for advanced or metastatic microsatellite stable colorectal cancer.

Primary Outcome Measures: Incidence of dose limiting toxicities (Safety lead in), Assessed by National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0., During cycle 1 (42 days)|Treatment related adverse event rates (Safety lead in), Assessed by NCI CTCAE version 5.0., During cycle 1 (42 days)|Response rate (Phase II) RECIST, Assessed by Response Evaluation Criteria in Solid Tumors (RECIST) version (v)1.1 (primary) in microsatellite stable metastatic colorectal cancer patients without metastatic liver lesions receiving botensilimab, balstilimab and regorafenib versus botensilimab and balstilimab, by treatment arm. Will be summarized by number, and percentage, along with Clopper-Pearson exact binomial confidence intervals., Up to 5 years after completion of study treatment|Response rate (Phase II) Immune-Modified RECIST, Assessed by Immune-Modified RECIST (secondary) in microsatellite stable metastatic colorectal cancer patients without metastatic liver lesions receiving botensilimab, balstilimab and regorafenib versus botensilimab and balstilimab, by treatment arm. Will be summarized by number, and percentage, along with Clopper-Pearson exact binomial confidence intervals., Up to 5 years after completion of study treatment
Secondary Outcome Measures: Overall survival, Will be estimated by the Kaplan-Meier method and calculated with 95% confidence intervals (CIs).

Will be summarized by number, and percentage, along with Clopper-Pearson exact binomial confidence intervals., From enrollment to death as a result of any cause or being censored at their last contact, assessed up to 5 years after completion of study treatment|Progression free survival, Will be estimated by the Kaplan-Meier method and will be calculated with 95% CIs.

Will be summarized by number, and percentage, along with Clopper-Pearson exact binomial confidence intervals., From enrollment to disease progression/relapse or death as a result of any cause, whichever occurs first, assessed up to 5 years after completion of study treatment|Duration of treatment response, Defined as time to progression or death, starting at the time when a response is experienced., Up to 5 years after completion of study treatment|Incidence of adverse events, Defined as toxicity, graded according to the NCI CTCAE v5.0. Toxicity data will be summarized in frequency tables by category and grade to evaluate the safety profile of the combination therapy., Up to 90 days after completion of study treatment