Merck Inc. files sBLA at FDA for Keytruda (pembrolizumab) to treat advanced microsatellite instability-high (MSI-H) cancer.

Merck Inc. has announced that the 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.

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.

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.