MedicalResearch.com Interview with: Scott Kopetz, M.D., Ph.D., FACP Associate Professor Department of Gastrointestinal Medical Oncology Division of Cancer Medicine The University of Texas MD Anderson Cancer Center Houston, TX MedicalResearch.com: What is the background for this study? What are the main findings? Response: The BRAF mutation carries a very poor prognosis for patients with advanced colo-rectal cancer (CRC), and is particularly unresponsive after first-line therapy, so additional treatment options for these patients are needed. While treatment with a BRAF inhibitor alone has not been effective in treating this disease, combination therapies have shown promise and lead to the initiation of the BEACON study. The safety lead-in phase of the BEACON CRC trial was designed to assess the safety and tolerability of encorafenib, binimetinib  and cetuximab triplet combination prior to the Phase 3 randomized portion of the study. Thirty patients were treated in the safety lead-in and received the triplet combination (encorafenib 300 mg daily, binimetinib 45 mg twice daily, and cetuximab per label). Out of the 30 patients, 29 had a BRAF^V600E mutation. Microsatellite instability-high (MSI-H) (resulting from defective DNA mismatch repair) was detected in only 1 patient. The triplet demonstrated good tolerability, supporting initiation of the randomized portion of the study. In addition, promising initial clinical activity was observed. In patients with the BRAF^V600E mutation, the estimated median progression-free survival (mPFS) at the time of analysis was 8 months. The confirmed overall response rate (ORR) in patients with the BRAF^V600E mutation was 48%, and 3 patients achieved complete responses (CR). Further, the ORR was 62% in the 16 patients (10/16) who received only one prior line of therapy. Additionally, the triplet combination was generally well-tolerated. Two patients discontinued treatment due to AEs with only one of these considered related to treatment. The most common grade 3 or 4 AEs seen in at least 10% of patients were fatigue (4/30), urinary tract infection (3/30), increased aspartate aminotransferase (AST; 3/30) and increased blood creatine kinase (CK; 3/30). (more…)