Merck, known as MSD outside the United States and Canada, announced that the US Food and Drug Administration (FDA) accepted for review the supplemental Biologics License Application (sBLA) for Keytruda (pembrolizumab), the company’s anti-PD-1 therapy, for the treatment of previously treated patients with advanced microsatellite instability-high (MSI-H) cancer. The FDA granted Priority Review with a PDUFA, or target action date, of March 8, 2017; the sBLA will be reviewed under the FDA’s Accelerated Approval program based on tumor response rate and durability of response. The FDA recently granted Breakthrough Therapy designation to Keytruda for unresectable or metastatic MSI-H non-colorectal cancer, and previously granted it for the treatment of patients with unresectable or metastatic MSI-H colorectal cancer.

“The FDA’s acceptance of this application represents an important advance for the field of immuno-oncology and is further evidence of Merck’s commitment to identifying patients most likely to benefit from Keytruda treatment,” said Dr. Roger M. Perlmutter, president, Merck Research Laboratories. “We believe that patients whose tumors harbor DNA repair defects may be especially responsive to Keytruda, and we look forward to working with the FDA to bring this important new therapy to these very challenging treatment situations.”

The application, which is seeking approval for Keytruda at a fixed dose of 200 mg every three weeks, is based on data from five uncontrolled, open-label, multi-cohort, multi-site phase I/II trials investigating the activity of Keytruda in MSI-H cancer.

Microsatellites are short repetitive sequences of DNA found throughout the genome. Microsatellite instability – or MSI – is caused by a deficiency in the cell’s ability to repair errors in the DNA sequence (mismatch repair) that occur during cell division leading to a characteristic change in microsatellite repeats. MSI-H is already an established biomarker in certain types of cancer. The presence of MSI is generally determined by an analytical test that compares the length of DNA from several microsatellite markers in tumor and normal cells, and produces a hallmark profile that distinguishes MSI-high, MSI-low, or microsatellite-stable tumor samples.

Keytruda is a humanized monoclonal antibody that works by increasing the ability of the body’s immune system to help detect and fight tumor cells. Keytruda blocks the interaction between PD-1 and its ligands, PD-L1 and PD-L2, thereby activating T lymphocytes which may affect both tumor cells and healthy cells.

Keytruda is administered as an intravenous infusion over 30 minutes every three weeks for the approved indications. Keytruda for injection is supplied in a 100 mg single use vial.

Keytruda is indicated for the treatment of patients with unresectable or metastatic melanoma at a dose of 2 mg/kg every three weeks until disease progression or unacceptable toxicity.

Keytruda is indicated for the first-line treatment of patients with metastatic non-small cell lung cancer (NSCLC) whose tumors have high PD-L1 expression [tumor proportion score (TPS) =50%] as determined by an FDA-approved test, with no EGFR or ALK genomic tumor aberrations.

Keytruda is also indicated for the treatment of patients with metastatic NSCLC whose tumors express PD-L1 (TPS =1%) as determined by an FDA-approved test, with disease progression on or after platinum-containing chemotherapy. Patients with EGFR or ALK genomic tumor aberrations should have disease progression on FDA-approved therapy for these aberrations prior to receiving Keytruda (pembrolizumab).

In metastatic NSCLC, Keytruda is administered at a fixed dose of 200 mg every three weeks until disease progression, unacceptable toxicity, or up to 24 months in patients without disease progression.

Keytruda is indicated for the treatment of patients with recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) with disease progression on or after platinum-containing chemotherapy. This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials. In HNSCC, Keytruda is administered at a fixed dose of 200 mg every three weeks until disease progression, unacceptable toxicity, or up to 24 months in patients without disease progression.