The US Food and Drug Administration (FDA) have granted a priority review for Merck’s anti-PD-1 agent pembrolizumab (Keytruda) as a first-line treatment of advanced melanoma, the company announced.¹

The FDA will review Merck’s supplemental biologics license application (sBLA) seeking approval of pembrolizumab as a frontline therapy for patients with unresectable or metastatic melanoma. The submission was based partly on data from the phase III KEYNOTE-006 clinical study of 834 patients, published in TheNew England Journal of Medicine on June 25, 2015.² The agency is expected to announce its final decision in December 19, 2015.

The KEYNOTE-006 trial found that pembrolizumab prolonged progression-free and overall survival, and those patients experienced lower rates of high-grade toxicity than patients administered ipilimumab (Yervoy) for advanced melanoma.

The FDA is separately reviewing Merck’s amended sBLA for pembrolizumab treatment of patients with ipilimumab-refractory advanced melanoma, and is expected to announce a final decision on that application by December 24, 2015.

“We have accumulated substantial data on the role of our anti-PD-1 therapy in advanced melanoma,” said Roger M. Perlmutter, MD, PhD, president of Merck Research Laboratories. “We look forward to the FDA’s review of each of these applications, and to delivering on our goal of helping patients with advanced melanoma to achieve long-term disease control and survival.”¹

Pembrolizumab is a humanized monoclonal antibody immune checkpoint inhibitor that targets the programmed cell death 1 (PD-1) receptor and thereby allows antitumor immune response. It is currently indicated in the United States at an intravenous dose of 2 mg/kg, infused over 30 minutes, every 3 weeks following progression of unresectable or metastatic melanoma following treatment with ipilimumab (and a BRAF inhibitor in patients whose tumors harbor a BRAF V600 mutation).

Toxicities can include fatigue, cough, nausea, diarrhea, rash, dyspnea, renal failure, and pneumonia. Patients should be monitored for pneumonitis, colitis, and thyroid, renal, and liver function.

Merck is conducting or has planned more than 100 clinical trials for pembrolizumab as a monotherapy, or as a component of combination therapies for more than 30 tumor types.

References:

• Merck & Co, Inc. (2015). FDA Accepts Supplemental Biologics License Application (sBLA) for KEYTRUDA® (pembrolizumab), Merck’s Anti-PD-1 Therapy, for First-Line Treatment of Advanced Melanoma, and Grants Priority Review.
• Robert C, Schachter J, Long GV, et al. (2015). Pembrolizumab versus Ipilimumab in Advanced Melanoma. The New England Journal of Medicine, Jun 25;372(26):2521-32.