Merck, a global healthcare leader, known as MSD outside the United States and Canada,  has submitted a supplemental Biologics License Application to the US Food and Drug Administration (FDA) for Keytruda (pembrolizumab), the company's anti-PD-1 therapy, for the treatment of advanced non-small cell lung cancer (NSCLC).

Keytruda previously received Breakthrough Therapy designation for advanced NSCLC and this initial filing seeks approval in the treatment of patients with advanced NSCLC whose disease has progressed on or after platinum-containing chemotherapy and an FDA-approved therapy for EGFR or ALK genomic tumor aberrations, if present.

Under PDUFA, the FDA has 60 days from submission of the sBLA to determine if the application will be accepted for review. The submission is based on data from Keynote-001 in patients with greater than or equal to 50 percent of tumor cells positive for PD-L1 expression. These data will be presented at the American Association for Cancer Research (AACR) annual meeting in Philadelphia.

“We are encouraged by the new Keynote-001 data evaluating Keytruda in patients with advanced non-small cell lung cancer, which will be presented at AACR annual meeting,” said Dr. Roger M. Perlmutter, president, Merck Research Laboratories. “We look forward to the FDAs review of our supplemental application for Keytruda, which is based in part on these data.”

A Premarket Approval Application (PMA) was submitted by Dako North America Inc, an Agilent Technologies Company, for an immunohistochemistry companion diagnostic test that detects PD-L1 expression, PD-L1 IHC 22C3 PharmDx.

Keytruda (pembrolizumab) is a humanized monoclonal antibody that blocks the interaction between PD-1 and its ligands, PD-L1 and PD-L2. By binding to the PD-1 receptor and blocking the interaction with the receptor ligands, Keytruda releases the PD-1 pathway-mediated inhibition of the immune response, including the anti-tumor immune response.

Keytruda is indicated in the United States at a dose of 2 mg/kg administered as an intravenous infusion over 30 minutes 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.

Merck is advancing a broad and fast-growing clinical development program for Keytruda with more than 85 clinical trials  across more than 30 tumor types and more than 14,000 patients  both as a monotherapy and in combination with other therapies.

Lung cancer, which forms in the tissues of the lungs, usually within cells lining the air passages, is the leading cause of cancer death worldwide. Each year, more people die of lung cancer than die of colon, breast, and prostate cancers combined. The two main types of lung cancer are non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC). NSCLC is the most common type of lung cancer, accounting for about 85 percent of all cases. The five-year relative survival rate for all advanced or metastatic (stage IV) lung cancers combined is estimated to be four percent.

PD-L1, also called programmed death-ligand 1, is a protein expressed on many types of cells, including some cancer cells. Under normal conditions, the interaction of PD-L1 with another protein, called programmed death receptor-1 (PD-1), serves as an important immune system checkpoint, keeping the immune system in balance and preventing the body from attacking its own cells when inflammation or an infection is present. When cancerous tumors express PD-L1, however, they are able to escape detection and destruction by cytotoxic T-cells  a type of cancer-killing immune cell  allowing the tumor to survive and grow.

Tumor PD-L1 expression has been observed at varying levels across many tumor types, including breast, lung and bladder cancer. Unnaturally high levels of PD-L1 expression, called overexpression, are under investigation for potential use as a way to help identify patients with an enhanced likelihood to respond to certain immune-based treatment approaches.