On October 27, 2014 Merck reported that the U.S. Food and Drug Administration (FDA) has granted Breakthrough Therapy Designation to KEYTRUDA (pembrolizumab), the company’s anti-PD-1 therapy, for the treatment of patients with Epidermal Growth Factor Receptor (EGFR) mutation-negative, and Anaplastic Lymphoma Kinase (ALK) rearrangement-negative non-small cell lung cancer (NSCLC) whose disease has progressed on or following platinum-based chemotherapy (Press release Merck & Co, OCT 27, 2014, View Source [SID:1234500883]). This is the second Breakthrough Therapy Designation granted for KEYTRUDA.

“The FDA’s Breakthrough Therapy Designation of KEYTRUDA underscores that new treatment approaches for advanced non-small cell lung cancer continue to be needed,” said Dr. Roger Perlmutter, president, Merck Research Laboratories. “Our data investigating the use of KEYTRUDA in this difficult-to-treat malignancy are very encouraging, and we look forward to working closely with the FDA to expedite our clinical program.”

KEYTRUDA is indicated in the United States at a dose of 2 mg/kg every three weeks for the treatment of patients with unresectable or metastatic melanoma and disease progression following ipilimumab and, if BRAF V600 mutation positive, a BRAF inhibitor. This indication is approved under accelerated approval based on tumor response rate and durability of response. An improvement in survival or disease-related symptoms has not yet been established. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.

The Breakthrough Therapy Designation in advanced NSCLC is supported by data from the ongoing Phase 1b KEYNOTE-001 study, and updated findings were recently presented at the European Society of Medical Oncology (ESMO) (Free ESMO Whitepaper) 2014 Congress. The FDA’s Breakthrough Therapy Designation is intended to expedite the development and review of a candidate that is planned for use, alone or in combination, to treat a serious or life-threatening disease or condition when preliminary clinical evidence indicates that the drug may demonstrate substantial improvement over existing therapies on one or more clinically significant endpoints. KEYTRUDA was previously granted breakthrough status for advanced melanoma.

KEYTRUDA is being studied across more than 30 types of cancers, as monotherapy and in combination. In advanced lung cancer, Merck is advancing a clinical program investigating the use of KEYTRUDA as monotherapy and in combination across lines of therapy and histology, including exploring different tumor characteristics such as PD-L1 expression as predictors of responsiveness. There are two ongoing Phase 2 and 3 studies in advanced lung cancer (KEYNOTE-010 and KEYNOTE-024) and an additional Phase 3 study is planned to begin in the fourth quarter of 2014 (KEYNOTE-042).