Date: 2016-06-04
Type of information: Presentation of results at a congress
phase: 2
Announcement: presentation of results at the American Society of Clinical Oncology (ASCO) annual meeting, in Chicago
Company: Array BioPharma (USA - CO)
Product: encorafenib and cetuximab
Action
mechanism: kinase inhibitor/BRAF inhibitor/monoclonal antibody. RAF is a protein kinase in the MAPK signaling pathway (RAS-RAF-MEK-ERK) that regulates several key cellular activities including proliferation, migration, survival and angiogenesis. Inappropriate activation of this pathway has been shown to occur in many cancers, such as melanoma, colorectal, lung and thyroid cancers. Encorafenib is a late-stage small molecule BRAF inhibitor, which targets key enzymes in this pathway. It is currently being studied in Phase 3 trials in advanced cancer patients, including the COLUMBUS trial studying encorafenib in combination with binimetinib in patients with BRAF-mutant melanoma and the recently initiated BEACON trial that will study encorafenib in combination with binimetinib and cetuximab in patients with BRAF V600E-mutant colorectal cancer. Array projects COLUMBUS top-line results availability during the third quarter of 2016. Cetuximab is a monoclonal antibody that binds specifically to the epidermal growth factor receptor (EGFR) on both normal and tumor cells. This antibody competitively inhibits the binding of epidermal growth factor.
Disease: patients with advanced BRAF-mutant colorectal cancer
Therapeutic area: Cancer - Oncology
Country:
Trial details:
Latest
news: * On June 4, 2016, Array BioPharma announced updated results from a Phase 2 study of the combination of encorafenib and cetuximab, with or without alpelisib, in patients with advanced BRAF-mutant colorectal cancer (BRAFm CRC). BRAFm CRC represents a difficult-to-treat subtype of colorectal cancer that impacts 8 to 15 percent of patients. Data from this study suggest that median overall survival (OS) for these patients may exceed one year which is more than double historical published benchmarks for this population. These data were presented at the 2016 American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago (Abstract No. 3544). In the Phase 2 study, 102 patients with BRAFm CRC who had progressed after one or more prior therapies were randomized to receive the doublet regimen of encorafenib and cetuximab (ENCO 200 mg PO QD and CETUX per label; n=50) or the triplet regimen of encorafenib, cetuximab and alpelisib (ENCO, CETUX and ALP 300 mg PO QD; n=52). The Phase 2 analysis for these treatment regimens demonstrated promising clinical activity in patients: Median OS was 12.4 and 13.1 months for the doublet and triplet regimens, respectively. With these encouraging results, Array also announced the initiation of a pivotal Phase 3 BEACON CRC (Binimetinib, Encorafenib And Cetuximab COmbiNed) to treat BRAF-mutant ColoRectal Cancer) global clinical trial, assessing the efficacy of binimetinib, encorafenib and cetuximab in comparison to cetuximab and irinotecan-based therapy.
Median progression-free survival (PFS) was 4.2 and 5.4 months for the doublet and triplet regimens, respectively.
Overall response rate (ORR) was 22 percent and 27 percent for the doublet and triplet regimens, respectively.
Grade 3 or 4 adverse events (AEs) occurring in greater than 10 percent of patients included anemia, hyperglycemia and increased lipase.
Historical published median PFS and median OS results after first-line treatment range from 1.8 to 2.5 months and four to six months, respectively, and published overall response rates from various studies in this population range between 6 percent to 8 percent.
