Date: 2016-09-14
Type of information: Initiation of the trial
phase: 3
Announcement: initiation of the trial
Company: Array BioPharma (USA - CO) Pierre Fabre (France) Merck KGaA (Germany)
Product: binimetinib, encorafenib and cetuximab
Action
mechanism: kinase inhibitor/RAF kinase inhibitor/MEK (MAP kinase) inhibitor/monoclonal antibody.The RAS/RAF/MEK/ERK pathway regulates several key cellular activities including proliferation, differentiation, migration, survival and angiogenesis. Inappropriate activation of proteins in this pathway has been shown to occur in many cancers, such as non-small cell lung cancer, melanoma, colorectal, ovarian and thyroid cancers. Binimetinib is a small molecule MEK inhibitor and encorafenib is a small molecule BRAF inhibitor, both of which target key enzymes in this pathway. 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. Array BioPharma is the owner of binimetinib and encorafenib. Pierre Fabre licensed commercial rights to binimetinib and encorafenib for Europe and other global markets from Array in December 2015.
Disease: metastatic colorectal cancer (mCRC)
Therapeutic area: Cancer - Oncology
Country:
Trial
details: BEACON CRC is a randomized, open-label, global study evaluating the efficacy and safety of binimetinib, encorafenib and Erbitux in patients with BRAFm metastatic CRC who have previously received first-line systemic therapy. Approximately 615 patients are expected to be randomized 1:1:1 to receive triplet therapy (binimetinib, encorafenib and Erbitux®), doublet therapy (encorafenib and Erbitux®) or the control arm (irinotecan-based therapy and Erbitux®). The primary endpoint of the trial is overall survival (OS) of the triplet therapy compared to the control arm. The secondary endpoints address efficacy of the doublet therapy compared to the control arm, and the triplet therapy compared to the doublet therapy. Other key secondary endpoints include progression-free survival (PFS), objective response rate (ORR), duration of response, safety and tolerability. Health related quality of life data will also be assessed. Array is conducting BEACON CRC in partnership with Pierre Fabre and Merck KGaA, Darmstadt, Germany at over 250 investigational sites in North America, South America, Europe and the Asia Pacific region. Patient enrollment is expected to be completed in 2018.
Latest
news: * On September 14, 2016, Array BioPharma announced that it has reached agreement with the FDA regarding a Special Protocol Assessment (SPA) related to BEACON CRC, a global Phase 3 trial of encorafenib and Erbitux® (cetuximab), with or without binimetinib, versus standard of care in patients with BRAF-mutant colorectal cancer (CRC) who have previously received first-or second-line systemic therapy. The SPA provides agreement that the design and planned analysis of BEACON CRC adequately address the objectives necessary to support a regulatory submission for the approval of the doublet regimen of encorafenib and Erbitux®. The FDA also communicated that sharing evidence from the study that the triplet regimen (encorafenib, Erbitux and binimetinib) both met its primary endpoint (Overall Survival) as compared to the control arm, and demonstrated a clinically meaningful benefit as compared to the doublet regimen, would provide support for approval of the triplet regimen. * On June 4, 2016, Array BioPharma, Pierre Fabre and Merck KGaA jointly initiated the BEACON CRC (Binimetinib, Encorafenib And Cetuximab Combined to treat BRAF-mutant Colorectal Cancer) trial, a randomized, global Phase 3 clinical trial designed to assess the safety and efficacy of binimetinib (MEK inhibitor), encorafenib (BRAF inhibitor) and Erbitux® (monoclonal antibody) in comparison to Erbitux® and irinotecan-based therapy in patients with BRAF-mutant colorectal cancer (BRAFm CRC). The primary endpoint is overall survival (OS) and key secondary endpoints include progression-free survival (PFS) and objective response rate (ORR). The trial will be conducted at over 250 investigational sites in North America, South America, Europe and the Asia Pacific region. Patient enrollment is expected to be completed in 2018. Array BioPharma is the owner of binimetinib and encorafenib and will act as the global sponsor of the study. Pierre Fabre licensed commercial rights to binimetinib and encorafenib for Europe and other global markets from Array in December 2015. As part of their collaboration, Pierre Fabre has elected to co-fund 40% of the cost of the BEACON CRC trial. Merck KGaA will supply Erbitux to all trial sites outside the United States and Canada as part of the collaboration. If successful, results would support regulatory submissions for all three parties.
