02-08-2018

Encorafenib and Binimetinib Combination Treatment Demonstrates 33.6 Month Median Overall Survival (OS) in Patients with BRAF-Mutant Melanoma in Phase 3 COLUMBUS Trial

Array BioPharma Inc. (Nasdaq: ARRY) and Pierre Fabre today announced results of the planned analysis of overall survival (OS) from the pivotal Phase 3 COLUMBUS trial in patients with BRAF-mutant melanoma. Treatment with the combination of encorafenib 450 mg daily and binimetinib 45 mg twice daily (COMBO450) reduced the risk of death compared to treatment with vemurafenib 960 mg twice daily [hazard ratio (HR) of 0.61, [95% CI 0.47, 0.79, p <0.001]. Median OS was 33.6 months for patients treated with COMBO450, compared to 16.9 months for patients treated with vemurafenib as a monotherapy. 

Many patients with BRAF-mutant melanoma still face significant challenges managing their disease, and there remains a substantial need for well-tolerated treatments that delay disease progression and improve overall survival, said Keith T. Flaherty, M.D., Director of the Termeer Center for Targeted Therapy, Massachusetts General Hospital Cancer Center and Professor of Medicine, Harvard Medical School. This data suggests that the combination of encorafenib and binimetinib may have the potential to become a meaningful new therapy for patients with advanced BRAF-mutant melanoma.

At the time of the planned analysis comparing COMBO450 to vemurafenib monotherapy, a preliminary analysis of OS in patients treated with 300 mg encorafenib alone daily (ENCO 300), demonstrated a median OS of 23.5 months.

We are excited to report these overall survival results from the COLUMBUS trial, said Victor Sandor, M.D., Chief Medical Officer, Array BioPharma. This encouraging overall survival finding further validates previously reported median progression-free survival and overall response rate results, and taken together with the attractive tolerability profile, these data suggest that the combination of encorafenib with binimetinib has the potential to become a promising new treatment option for these patients.

In light of these results, Frédéric Duchesne, President & CEO of Pierre Fabre Médicament & Santé, commented: We are particularly pleased with these results. They confirm that the combination of Encorafenib and Binimetinib currently being registered represents a real therapeutic chance for patients suffering from one of the most severe forms of melanoma, a cancer that is unfortunately rapidly spreading. These overall survival results will allow us to supplement the registration dossiers filed with the European and Australian authorities. In addition, we continue to develop with Array BioPharma the combination in colorectal cancer in order to benefit as quickly as possible patients waiting for new therapeutic solutions.

As previously reported, the combination of encorafenib and binimetinib was generally well-tolerated. Grade 3/4 adverse events (AEs) that occurred in more than 5% of patients receiving the combination were increased gamma-glutamyltransferase (GGT) (9%), increased blood creatine phosphokinase (CK) (7%) and hypertension (6%). The incidence of selected any grade AEs of special interest, defined based on toxicities commonly associated with commercially available BRAF+MEK-inhibitor treatments for patients receiving the combination of encorafenib and binimetinib included: rash (23%), pyrexia (18%), retinal pigment epithelial detachment (13%) and photosensitivity (5%). Full safety results of COLUMBUS Part 1 were presented at the 2016 Society for Melanoma Research Annual Congress.

The U.S. Food and Drug Administration (FDA) is currently reviewing the New Drug Applications to support use of the combination of encorafenib and binimetinib for the treatment of patients with BRAF-mutant advanced, unresectable or metastatic melanoma. The FDA set a target action date under the Prescription Drug User Fee Act (PDUFA) of June 30, 2018 for both applications. In addition, the European Medicines Agency (EMA), as well as the Swiss Medicines Agency (Swissmedic) and the Australian Therapeutic Goods Administration (TGA), is reviewing the Marketing Authorization Applications for encorafenib and binimetinib.

A detailed update from the COLUMBUS trial will be presented at an upcoming medical congress.

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