The United States Food and Drug Administration (FDA) has approved the use of trametinib (Mekinist®) in combination with dabrafenib (Tafinlar®) for treatment of unresectable melanoma or metastatic melanoma with BRAF V600E or V600K mutations that are detected by an FDA-approved test, according to a press release from GlaxoSmithKline.

The combination received priority review and was approved via the FDA’s Accelerated Approval Program.  Approval remains dependent on results of an ongoing phase 3 trial evaluating the clinical benefit of the combination treatment in the indicated patient population.

According to the statement released today, approval was based on results from a phase 1/2 study designed to assess the combination of dabrafenib and trametinib at the recommended dose of 150 mg/2 mg versus a 150-mg dose of dabrafenib alone.

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Data from the randomized phase 2 component of the phase 1/2 open-label study demonstrated an overall response rate of 76% (95% CI: 62%-87%) in the combination treatment arm versus 54% (95% CI: 40%-67%) in the dabrafenib-alone arm. Results also revealed a median duration of response of 10.5 months (95% CI: 7-15 months) in the combination treatment arm versus 5.6 months (95% CI: 5-7 months) in the dabrafenib-alone arm.

According to the release, a blinded independent radiologic review committee supported the study findings. Their analyses showed an overall response rate of 57% (95% CI: 43%-71%) in the combination treatment arm versus 46% (95% CI: 33%-60%) in the dabrafenib-alone arm and a median duration of response of 7.6 months (95% CI: 7 months-not reported) in the combination treatment arm versus 7.6 months (95% CI, 6 months-not reported) in the dabrafenib-alone arm.

The most frequently occurring adverse reactions were pyrexia, chills, fatigue, rash, nausea, vomiting, diarrhea, abdominal pain, edema peripheral, cough, headache, arthralgia, night sweats, decreased appetite, constipation, and myalgia.

Combination treatment with trametinib and dabrafenib is associated with serious side effects, including new primary cutaneous malignancies, tumor promotion in wild-type BRAF melanoma, hemorrhagic events, venous thromboembolic events, cardiomyopathy, ocular toxicities, interstitial lung disease, febrile drug reactions, serious skin toxicity, hyperglycemia, hemolytic anemia in patients with glucose-6-phosphate dehydrogenase deficiency and embryofetal toxicity.

“This approval marks another key moment in what continues to be a rapid evolution of the treatment landscape for metastatic melanoma patients. Combining agents that target different mechanisms regulating the growth of cancer cells is one of the promising areas in cancer research,” Paolo Paoletti, MD, President of Oncology at GlaxoSmithKline, said in the release.

“We are proud that the first approved combination of targeted therapies in metastatic melanoma patients is Mekinist and Tafinlar, and our hope is that it will become part of the new standard of care for appropriate patients with BRAF V600E or V600K mutation-positive metastatic melanoma.”