Lung Cancer Drug Granted Breakthrough Therapy Designation by FDA

The FDA today granted breakthrough therapy designation to a new treatment for non-small cell lung cancer patients whose disease has progressed on or following platinum-based chemotherapy.

Merck’s pembrolizumab (Keytruda) is an anti-PD-1 therapy for patients with Epidermal Growth Factor Receptor (EGFR) mutation-negative and Anaplastic Lymphoma Kinase (ALK) rearrangement-negative non-small cell lung cancer. Pembrolizumab was previously granted breakthrough therapy designation for the treatment of advanced melanoma.

“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 Roger Perlmutter, MD, president of Merck Research Laboratories, in a press release. “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.”

Pembrolizumab is administered at a dose of 2 mg/kg every 3 weeks in patients with unresectable or metastatic melanoma and disease progression following ipilimumab and a BRAF inhibitor in those who are BRAF V600 mutation-positive. Although it was granted accelerated approval based on its tumor response rate and the durability of response, it has not yet been established whether the drug provides improvement in survival or disease-related symptoms.

Pembrolizumab acts as a humanized monoclonal antibody that blocks the interaction between PD-1 and its PD-L1 and PD-L2 ligands. Through the process of binding to the PD-1 receptor, which blocks interaction with the receptor ligands, the PD-1 pathway-mediated inhibition of the immune response is released, including anti-tumor immune response.

The continued approval for pembrolizumab may depend upon verification and description of clinical benefit in subsequent confirmatory trials.

Pembrolizumab is currently being evaluated across more than 30 types of cancers, both as a monotherapy and combination treatment. For the treatment of advanced lung cancer, a clinical trial examining the use of pembrolizumab as monotherapy and in combination across lines of therapy and histology—including different tumor characteristics, such as PD-L1 expression as predictors of responsiveness—is advancing.

During a clinical trial with 411 advanced melanoma patients, adverse events included pneumonitis (2.9%), colitis (1%), hepatitis (0.5%), hypophysitis (0.5%), nephritis (0.7%), and hyperthyroidism (1.2%).

In addition to 2 ongoing phase 2 and 3 studies for advanced lung cancer, an additional phase 3 study is expected to begin in the fourth quarter of 2014.