Regorafenib and Pembrolizumab in Treating Participants With Advanced or Metastatic Colorectal Cancer

This phase I/II studies the side effects and best dose of regorafenib when given together with pembrolizumab in treating participants with colorectal cancer that has spread to other places in the body. Drugs used in chemotherapy, such as regorafenib, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Monoclonal antibodies, such as pembrolizumab, may interfere with the ability of tumor cells to grow and spread. Giving regorafenib and pembrolizumab may work better at treating colorectal cancer.

PRIMARY OBJECTIVES: I. To assess safety of the combination and identification of the recommended dose (RD) for combination therapy. (Phase I) II. To evaluate preliminary efficacy and tolerability of the combination RD of regorafenib and pembrolizumab. (Phase II) EXPLORATORY OBJECTIVES: I. The associations between biomarkers and clinical outcome will be investigated. OUTLINE: This is a phase I, dose-escalation study of regorafenib followed by a phase II study. Participants receive pembrolizumab intravenously (IV) over 30 minutes on day 1 and regorafenib orally (PO) once daily (QD) on days 1-14. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, participants are followed up periodically.