Combining low-dose regorafenib with pembrolizumab for patients with MSI-H colorectal cancer: REGPEM-CRC-01.

• DOI: 10.1200/jco.2025.43.4_suppl.tps313
• Publication Date: 2025-01-27T14:30:16Z
• Authors: Ibrahim Halil Sahin; Ronan Wenhan Hsieh; Vikram Gorantla; Stacey A. Cohen; John C. Rhee; Rachael A. Safyan; Curtis Tatsuoka; E. Gabriela Chiorean; Mohamedtaki Abdul...; Al B. Benson; Patrick M Boland; Richard D. Kim; Anwaar Saeed
• Keywords: Regorafenib

TPS313 Background: Currently, pembrolizumab is one of the front-line therapies for patients with MSI-H CRC. However, approximately 40% who received experienced disease progression early in course (KEYNOTE 177). Therefore, there still an unmet need to enhance efficacy checkpoint inhibitors CRC has a higher level expression VEGF blood compared its MSS counterpart (Hansen et al. Colorectal Dis. 2011). Consistently, exploratory analysis CALBG-80405 and PARADIGM trial showed that were more likely benefit from anti-VEGF therapy than anti-EGFR regardless side tumor. NSABP C-08 also suggested may have biological activity even as adjuvant colon cancer. Regorafenib potent inhibitor, preclinical evidence showing immune modulatory effect tumor microenvironment. In this trial, we hypothesize adding low-dose regorafenib induce synergistic beyond their independent clinical create deep durable responses Methods: lead arm prospective randomized study, 22 will be enrolled through Hoosier Cancer Research Network (HCRN-GI23-643). Patients treatment naïve trial. One cycle up 3 cycles chemotherapy prior determination MMR-D/MSI-H allowed. receive 60 mg daily combination 200mg IV 1, followed by 90mg subsequent improve tolerance. The primary outcome measured ORR, defined percentage partial or complete response within 12 months. ORR using RECIST 1.1. criteria. A formal one-sided hypothesis test conducted futility, assuming reject null target only if strong evidence. assume 0.60, which would reflect significant improvement over current standard = 0.43 KEYNOTE 177. alternative less 0.60. For lead-in phase emphasis on controlling Type I error small, 0.05. statistic number ORRs patients, follow binomial distribution. Clinical information: NCT06006923 .