Phase 3 BEACON CRC Safety Lead-In Results in BRAF-Mutant Colorectal Cancer Presented at European Society for Medical Oncology Congress
- 41% confirmed ORR for patients on combination of binimetinib, encorafenib and cetuximab
- Median duration of treatment was 5.6 months at time of analysis and 76% of patients remain on study treatment
- Generally well-tolerated with attractive safety profile
- Array to host investor reception and webcast during ESMO on September 9
Boulder, Colo. US, Castres, France (September 8, 2017) Array BioPharma (Nasdaq: ARRY) and Pierre Fabre today announced safety results and initial clinical activity from the safety lead-in of the Phase 3 BEACON CRC study evaluating binimetinib, a MEK inhibitor, encorafenib, a BRAF inhibitor and Erbitux (cetuximab), an anti-EGFR antibody, in patients with BRAF-mutant colorectal cancer (CRC) whose disease has progressed after one or two prior regimens in the metastatic setting. BRAF-mutant CRC represents a difficult-to-treat subtype of colorectal cancer that impacts 10 to 15% of CRC patients. These data were presented as an e-poster on September 8 at the 2017 European Society for Medical Oncology Congress in Madrid, Spain (Abstract No. #517P).
As of August 9, 2017, 30 patients were treated in the safety lead-in and received the triplet combination of binimetinib, encorafenib and cetuximab (BINI 45 mg twice daily, ENCO 300 mg daily and CETUX per label). Out of the 30 patients, 29 had a BRAFV600E mutation. Microsatellite instability-high (MSI-H) (resulting from defective DNA mismatch repair) was detected in only one patient. The triplet demonstrated good tolerability, supporting initiation of the randomized portion of the study. In addition, promising initial clinical activity was observed, with a confirmed overall response rate (ORR) of 41%, including a complete response, in patients with the BRAF mutation, a group of patients with historically poor outcomes. The observed ORR was 59% in the 17 patients with the BRAF mutation with only one prior therapy.Â Out of 28 patients with both a BRAFV600E mutation and a post-baseline assessment, 27 showed tumor regression.
« The BRAF mutation carries a very poor prognosis for patients with advanced colorectal cancer, and is particularly unresponsive after first-line therapy, » said 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. â€œIn the safety lead-in, the triplet combination showed impressive results with a confirmed overall response rate of 41%. Several patients also showed prolonged stable disease, with 76% of patients overall continuing on therapy after a median duration of exposure of 5.6 months. These results are unprecedented for this patient population based on existing standards of care.
In the safety lead-in, the triplet combination was generally well-tolerated. The most common grade 3 or 4 adverse events (AEs) seen in at least 10% of patients were nausea (10%), vomiting (10%), increased blood creatine kinase (10%) and urinary tract infection (10%). Three patients discontinued treatment due to AEs with only one considered related to treatment. At the time of the analysis, 76% of patients remain on study treatment after a median duration of treatment of 5.6 months (range 1.0 – 9.3 months).
With these encouraging results, Array continues to enroll the randomized portion of the BEACON CRC study, assessing the efficacy of encorafenib in combination with cetuximab with or without binimetinib compared to cetuximab and irinotecan-based therapy.
« There has been a long-standing need to find improved treatment options for patients with BRAF-mutant colorectal cancer, and we are encouraged that data from the safety lead-in show binimetinib, encorafenib and cetuximab may have this potential, » said Axel Grothey, M.D., Professor of Oncology, Mayo Clinic College of Medicine and Science. « We hope these promising findings, with the impressive response rates, including a complete response, and early signs of durability, will bring us one step closer to addressing this high unmet medical need ».