Fast-Track Approval for New Melanoma Combination Treatment

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PHILADELPHIA — Accelerated approval has been granted by the Food and Drug Administration to a combination therapy for unresectable or metastatic melanoma with a specific mutation.

Approval was announced of a trametinib-dabrafenib combination for use in the treatment of patients with unresectable or metastatic melanoma with a BRAF V600E or V600K mutation as detected by an FDA-approved test.

Trametinib is marketed as Mekinist tablets and dabrafenib is marketed as Tafinlar capsules, both by GlaxoSmithKline.

In 2013, trametinib was previously approved as a single agent for treatment of BRAF V600E or V600K mutation-positive unresectable or metastatic melanoma, and dabrafenib was approved as a single agent for treatment of BRAF V600E mutation-positive unresectable or metastatic melanoma. Trametinib and dabrafenib target two different tyrosine kinases in the RAS/RAF/MEK/ERK pathway.

FDA approval of the combination therapy was based on the demonstration of durable objective responses in a multicenter, open-label, randomized, active-controlled, dose-ranging trial enrolling 162 patients with histologically confirmed Stage IIIC or IV melanoma determined to be BRAF V600E or V600K.

The agency noted, however, that granting of the accelerated approval is contingent upon the successful completion of an ongoing MEK115306 trial to verify the clinical benefit of trametinib for use in combination with dabrafenib. MEK115306 is an international, multicenter, randomized (1:1), double-blind, placebo-controlled trial comparing the combination of dabrafenib and trametinib to dabrafenib and placebo as first-line therapy in approximately 340 patients with Stage IIIC or Stage IV BRAF V600E or V600K mutation-positive cutaneous melanoma.

The recommended dose and schedule for trametinib and dabrafenib when used in combination is trametinib 2 mg orally once daily with dabrafenib 150 mg orally twice daily continued until disease progression or unacceptable toxicity occurs. The drugs should be taken at least one hour before or two hours after a meal, and the once daily dose of trametinib can be taken at the same time as either dose of dabrafenib.

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