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Merck Seeks Additional FDA Approval for Keytruda (Pembrolizumab) in Advanced Lung Cancer

Treatment currently indicated for melanoma

Merck has submitted a supplemental biologics license application (sBLA) to the FDA for Keytruda (pembrolizumab), the company’s anti-programmed death-1 (PD-1) therapy, for the treatment of advanced non–small-cell lung cancer (NSCLC). Pembolizumab previously received a “breakthrough therapy” designation for advanced NSCLC, and this initial filing seeks approval for the treatment of patients with advanced NSCLC whose disease has progressed on or after platinum-containing chemotherapy and an FDA-approved therapy for epidermal growth factor receptor (EGFR) or anaplastic lymphoma kinase (ALK) genomic tumor aberrations, if present.

Under the Prescription Drug User Fee Act, the FDA has 60 days from submission of the sBLA to determine whether the application will be accepted for review. The submission is based on data from the KEYNOTE-001 trial in patients with greater than or equal to 50% of tumor cells that are positive for programmed death ligand-1 (PD-L1) expression. These data were presented April 19 at the American Association for Cancer Research (AACR) annual meeting in Philadelphia, Pennsylvania.

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

PD-L1 is a protein expressed on many types of cells, including some cancer cells. Under normal conditions, the interaction of PD-L1 with 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 immune cell –– thereby allowing the tumor to survive and grow. The expression of PD-L1 in tumors has been observed across several tumor types, including breast, lung, and bladder cancer. The over-expression of PD-L1 is under investigation for its potential use as a way to help identify patients with an enhanced likelihood of responding to certain immune-based treatment approaches.

Keytruda (pembrolizumab) is indicated in the U.S. at a dosage of 2 mg/kg administered as an intravenous infusion over 30 minutes every 3 weeks for the treatment of patients with unresectable or metastatic melanoma and disease progression after treatment with ipilimumab (Yervoy, Bristol-Myers Squibb) and, if BRAF V600 mutation-positive, a BRAF inhibitor. This indication was based on the tumor response rate and the durability of response. An improvement in survival or disease-related symptoms has not been established. Continued approval for this indication may be contingent on the verification and description of clinical benefit in confirmatory trials.

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 NSCLC and small-cell lung cancer (SCLC). NSCLC is the most common type of lung cancer, accounting for approximately 85% of all cases. The 5-year relative survival rate for all advanced or metastatic (stage IV) lung cancers combined is estimated to be 4%.

Source: PipelineReview; April 20, 2015.

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