FDA approves Mekinist/Tafinlar combination for melanoma

The FDA recently approved trametinib combined with dabrafenib for treatment of patients with unresectable melanoma or metastatic melanoma with BRAF V600E or V600K mutations.

FDA approval for the combination was based on the demonstration of response rate and median duration of response in a phase 1/2 study and approved through the FDA’s accelerated approval program and reviewed under a priority review designation. However, this accelerated approval is contingent on results of an ongoing phase 3 trial (MEK115306), designed to assess the clinical benefit of the combination in this patient population.

Improvement in disease-related symptoms or OS has not been demonstrated for trametinib (Mekinist) combined with dabrafenib (Tafinlar).

Paolo Paoletti

“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 a press release. “We are proud that the first approved combination of targeted therapies in metastatic melanoma 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.”

The results from the randomized phase 2 part of the phase 1/2 open-label study, which evaluated the combination of trametinib and dabrafenib at the recommended dose (150 mg dabrafenib twice daily, 2 mg trametinib once daily; n=54) and single-agent dabrafenib (150 mg; n=54), included:

The investigator-assessed overall response rate (ORR) was 76% (95% CI, 62-87) for patients treated with the combination, and 54% (95% CI, 40-67) for patients treated with single-agent dabrafenib. The median duration of response was 10.5 months (95% CI, 7-15) for patients treated with the combination and 5.6 months (95% CI, 5-7) for patients treated with single-agent dabrafenib.
Data analyses of the masked independent radiologic review committee supported the investigator results. The committee-assessed ORR was 57% (95% CI, 43-71) for patients treated with the combination and 46% (95% CI, 33-60) for patients receiving single-agent dabrafenib. The median duration of response as assessed by the committee was 7.6 months for patients treated with the combination and for those treated with single-agent dabrafenib.

The most common (≥2%) grade 3 or 4 adverse events observed in the combination group at the recommended dose of trametinib 2 mg once daily combed with dabrafenib 150 mg twice daily in this study included: renal failure (7%), pyrexia (5%), back pain (5%), hemorrhage (5%), fatigue (4%), chills (2%), nausea (2%), vomiting (2%), diarrhea (2%), abdominal pain (2%), myalgia (2%) and urinary tract infection (2%).