FDA Approves Keytruda for Metastatic Non-Small Cell Lung Cancer

The US Food and Drug Administration (FDA) today announced that it has granted accelerated approval for Merck’s anti-PD-1 agent pembrolizumab (Keytruda) for treating patients with refractory metastatic non-small cell lung cancer (NSCLC) tumors that express programmed cell death protein ligand 1 (PD-L1).

It is the first drug approved for patients whose lung tumors express PD-L1, the agency reported. Pembrolizumab is approved for use with the diagnostic PD-L1 HIS 22C3 pharmDx test to detect PD-L1 expression in NSCLC tumors.

“Our growing understanding of underlying molecular pathways and how our immune system interacts with cancer is leading to important advances in medicine,” commented Richard Pazdur, MD, director of the Office of Hematology and Oncology Products at the FDA’s Center for Drug Evaluation and Research.

“Today’s approval of Keytruda gives physicians the ability to target specific patients who may be most likely to benefit from this drug,” he said.

Pembrolizumab is a humanized monoclonal antibody immune checkpoint inhibitor that targets the programmed cell death 1 (PD-1) receptor to facilitate antitumor immune response. Its effectiveness was demonstrated in a subgroup of 61 patients with NSCLC whose PD-L1-positive tumors had progressed following platinum-based chemotherapy or targeted therapy for tumors harboring ALK or EGFR mutations, the FDA announcement stated. Those patients received 10 mg/kg of pembrolizumab every 2 or 3 weeks. Their overall response rate was 41% and responses were durable, lasting between 2.1 and 9.1 months, the FDA reported.

Pembrolizumab’s safety was studied in 550 patients with advanced NSCLC. Common toxicities were found to include fatigue, dyspnea (shortness of breath) and cough, and decreased appetite. It can also cause severe immune-mediated toxicities in the lungs, colon, and hormone-producing glands. Vasculitis (immune-mediated vascular inflammation) was also an uncommon side effect.

“Women who are pregnant or breastfeeding should not take Keytruda because it may cause harm to a developing fetus or newborn baby,” the FDA announcement cautioned. “Across clinical studies, a disorder in which the body’s immune system attacks part of the peripheral nervous system (Guillain-Barre syndrome) also occurred.”

In 2014, pembrolizumab was approved by the FDA for treating patients with advanced melanoma after treatment with ipilimumab immunotherapy. Nivolumab similarly targets the PD-1/PD-L1 pathway and was approved for treatment of squamous NSCLC earlier this year.

The FDA granted pembrolizumab breakthrough therapy designation for metastatic PD-L1-expressing NSCLC based on Merck’s demonstration through preliminary clinical evidence that it may offer “a substantial improvement over available therapies,” the agency announced. “The drug also received priority review status, which is granted to drugs that, at the time the application was submitted, have the potential to be a significant improvement in safety or effectiveness in the treatment of a serious condition.”

Merck is conducting or has planned more than 100 clinical trials for pembrolizumab monotherapy and combination therapy, for more than 30 tumor types.