FDA grants priority review to Tafinlar plus Mekinist for adjuvant treatment of BRAF-positive melanoma

The FDA granted priority review to dabrafenib in combination with trametinib for the adjuvant treatment of patients with stage III melanoma who harbor BRAF V600E or V600K mutations.

If approved, dabrafenib (Tafinlar, Novartis), a BRAF inhibitor, plus trametinib (Mekinist, Novartis), a MEK 1/2 inhibitor, would be the first adjuvant targeted therapy combination to demonstrate a significant clinical benefit for patients with a BRAF V600 mutation.

As HemOnc Today previously reported, this application also received breakthrough therapy designation.

“The FDA’s decision to grant Tafinlar in combination with Mekinist breakthrough therapy designation and priority review designation validates the potential of the combination to have a significant impact on the lives of melanoma patients treated in the adjuvant setting,” Samit Hirawat, MD, head of Novartis Oncology Global Drug Development, said in a press release. “There remains a need to address the high risk [for] recurrence seen in these patients and improve the quality of care they receive.”

The FDA based this decision on data from the COMBI-AD phase 3 study of the combination among 870 patients with stage III BRAF V600E/V600K mutation-positive melanoma who underwent resection.

Compared with placebo, the combination conferred a 53% decrease in the risk for disease recurrence or death (HR = 0.47; 95% CI, 0.39-0.58), and improved OS (HR = 0.57; 95% CI, 0.42-0.79), although the latter did not reach the predefined interim analysis boundary for statistical significance.

The most common side effects associated with combination therapy are fever, nausea, diarrhea, fatigue, chills, headache, vomiting, joint pain, high blood pressure, rash and cough.