FDA grants accelerated approval for Keytruda (pembrolizumab)for the treatment of adult and pediatric patients with unresectable or metastatic, microsatellite instability-high (MSI-H) or mismatch repair deficient solid tumors - Merck Inc.

Merck has announced that the FDA has approved a new indication for Keytruda (pembrolizumab), the company’s anti-PD-1 therapy. Keytruda is now indicated for the treatment of adult and pediatric patients with unresectable or metastatic, microsatellite instability-high (MSI-H) or mismatch repair deficient solid tumors that have progressed following prior treatment and who have no satisfactory alternative treatment options, or colorectal cancer that has progressed following treatment with a fluoropyrimidine, oxaliplatin, and irinotecan. 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.

The safety and effectiveness of Keytruda in pediatric patients with MSI-H central nervous system cancers have not been established. The recommended dose of Keytruda in adults is 200 mg administered as an intravenous infusion over 30 minutes every three weeks until disease progression, unacceptable toxicity, or up to 24 months in patients without disease progression. In children, the recommended dose of Keytruda is 2 mg/kg (up to a maximum of 200 mg) administered as an intravenous infusion over 30 minutes every three weeks until disease progression or unacceptable toxicity, or up to 24 months in patients without disease progression.

Comment: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.

Comment:This is the first time the agency has approved a cancer treatment based on a common biomarker rather than the location in the body where the tumor originated.