Novartis today announced that the US Food and Drug Administration (FDA) has granted Breakthrough Therapy Designation (BTD) for Tafinlar® (dabrafenib) in combination with Mekinist® (trametinib) for the adjuvant treatment of patients with stage III melanoma with a BRAF V600 mutation following complete resection. Tafinlar in combination with Mekinist is in development to become the first adjuvant treatment specifically for melanoma patients with a BRAF V600 mutation.

The designation is based on results from COMBI-AD, a Phase III study of 870 patients with stage III BRAF V600E/K mutation-positive melanoma after complete surgical resection treated with Tafinlar + Mekinist[1]. Patients received the Tafinlar (150 mg BID) + Mekinist (2 mg QD) combination (n = 438) or matching placebos (n = 432)[1]. After a median follow-up of 2.8 years, the primary endpoint of relapse-free survival (RFS) was met. Treatment with the combination therapy significantly reduced the risk of disease recurrence or death by 53% vs. placebo (HR: 0.47 [95% CI: 0.39-0.58]; median not reached vs. 16.6 months, respectively; p<0.001)[1]. The RFS benefit among the combination arm was observed across all patient subgroups, including stage III A, B and C[1]. These results were recently presented at the European Society for Medical Oncology Congress (ESMO) and published in the New England Journal of Medicine[1],[2].

"There is a need for more effective treatment options for stage III melanoma patients at a high risk of recurrence following surgical resection," said Samit Hirawat, Executive Vice President and Head, Global Drug Development at Novartis Oncology. "We thank the FDA for recognizing the scientific advancement Tafinlar and Mekinist may provide in this adjuvant setting."

Adverse events (AEs) were consistent with other Tafinlar + Mekinist studies, and no new safety signals were reported[1]. Of patients treated with the combination, 97% experienced an AE; 41% had grade 3/4 AEs and 26% had AEs leading to treatment discontinuation (vs. 88%, 14% and 3%, respectively, with placebo)[1].

According to FDA guidelines, treatments that receive Breakthrough Therapy Designation are those that treat a serious or life threatening disease or condition and demonstrate a substantial improvement over existing therapies on one or more clinically significant endpoints based on preliminary clinical evidence. The designation also indicates that the agency will expedite the development and review of Tafinlar + Mekinist for the adjuvant treatment of patients with stage III melanoma with a BRAF V600 mutation following complete resection. The treatment combination has previously received Breakthrough Therapy Designations in metastatic melanoma, non-small cell lung cancer (NSCLC) and anaplastic thyroid cancer (ATC).