European Commission approves Tafinlar in combination with Mekinist for the adjuvant treatment of stage III patients with BRAF V600 mutation-positive melanoma after complete surgical resection.- Novartis.

Novartis announced that the European Commission (EC) has approved Tafinlar (dabrafenib) in combination with Mekinist (trametinib) for the adjuvant treatment of stage III patients with BRAF V600 mutation-positive melanoma after complete surgical resection. This approval is the third for Tafinlar in combination with Mekinist in Europe across a variety of tumor types identified with a high level of BRAF mutation. It also demonstrates Novartis leadership in BRAF+ targeted therapy, and to date, more than 60,000 patients worldwide have been treated with the combination therapy across four indications.

The approval is based on results from the Phase III COMBI-AD global study, which enrolled more than 870 patients with stage III, BRAF V600E/K-mutant melanoma without prior anticancer therapy, and who were randomized within 12 weeks of complete surgical resection. Patients received the Tafinlar (150 mg BID) + Mekinist (2 mg QD) combination (n = 438) or matching placebos (n = 432). In the primary analysis, and after a median follow-up of 2.8 years, the primary endpoint was met, with the combination therapy significantly reducing the risk of disease recurrence or death by 53% vs. placebo. Based on updated data, with an additional 10 months of follow-up compared to the primary analysis (minimum follow-up of 40 months), treatment with the combination therapy reduced the risk of recurrence or death by 51% vs. placebo. Additionally, the relapse free survival (RFS) benefit among the combination arm was observed across all patient subgroups, including stage III A, B and C. The combination treatment group also saw an improvement in a key secondary endpoint of overall survival. The BRAF gene belongs to a class of genes known as oncogenes and provides instructions for making a protein that helps transmit chemical signals from outside the cell to the cell's nucleus. This protein is part of a signaling pathway known as the RAS/MAPK pathway, which controls several important cell functions.

Specifically, the RAS/MAPK pathway regulates the growth and division (proliferation) of cells, the process by which cells mature to carry out specific functions (differentiation), cell movement (migration) and the self-destruction of cells (apoptosis). Chemical signaling through this pathway is essential for normal development before birth. When mutated, oncogenes have the potential to cause normal cells to become cancerous. During cancer treatment, targeted therapies may inhibit the mutation from occurring, thus slowing the growth of the cancer tumor.

Adverse events (AEs) were consistent with other Tafinlar + Mekinist studies and no new safety signals were reported. Of patients treated with the combination, 97% experienced an AE, with 41% having grade 3/4 AEs and 26% having AEs leading to treatment discontinuation (vs. 88%, 14%, and 3%, respectively, with placebo).