Safety and efficacy of encorafenib, binimetinib, plus cetuximab for BRAF V600E-mutant metastatic colorectal cancer: Results of a prospective study as an expanded access program.

Abstract

199 Background: The encorafenib, binimetinib, and cetuximab (triplet) regimen showed survival benefit and a higher response rate over standard chemotherapy among pretreated patients (pts) with BRAF V600E-mutant metastatic colorectal cancer (mCRC) in the phase III BEACON trial. Herein, we report the safety and efficacy of the triplet regimen in a prospective study (JapicCTI-205146) as a Japanese expanded access program (EAP). Methods: The key eligibility criteria were age ≥18 years and a diagnosis of BRAF V600E-mutant mCRC with progression observed after one or two prior systemic chemotherapy. Encorafenib (300 mg QD), binimetinib (45 mg BID), and weekly cetuximab (400 mg/m2, followed by 250 mg/m2) were administered. Patients who had received at least one dose of any study drug were included in this analysis. Adverse events were evaluated using CTCAE v4.0. The objective response rate (ORR) was evaluated using RECIST Guideline Version 1.1. Results: A total of 86 pts were enrolled from 10 Japanese institutions from February to December 2020. Safety and efficacy were evaluated in 81 pts. The median age was 60 years. Fifty-four pts (67%) had ECOG PS 0 and 50 pts (62%) received one prior chemotherapy. Treatment-related serious adverse events and grade 3 or higher treatment-related adverse events were observed in 14 (17%) and 24 (30%) pts, respectively. Treatment-related death occurred in one pts. Among the 76 pts with target lesions, 21 pts were responders, and the confirmed ORR was 27.6%. Stable disease was observed in 42 pts, resulting in a disease control rate of 82.9%. The ORR was consistent regardless of ECOG PS status, the number of prior chemotherapy lines, and the number of metastatic organs. Conclusions: The safety and efficacy of the triplet regimen in the Japanese EAP were comparable to those in the BEACON trial. These results support the triplet regimen as a new standard-of-care treatment option in the second- or third-line treatment of pts with BRAF V600E-mutant mCRC in the Japanese population, as there was a promising response without any new safety signals. Clinical trial information: JapicCTI-205146.