Keytruda filed at FDA to treat patients with unresectable or metastatic solid tumors with tissue tumor mutational burden-high.- Merck Inc.

-Merck Inc., has announced that the FDA has accepted and granted priority review for a new supplemental Biologics License Application (sBLA) for Keytruda, Merck’s anti-PD-1 therapy. The application seeks accelerated approval of Keytruda monotherapy for the treatment of adult and pediatric patients with unresectable or metastatic solid tumors with tissue tumor mutational burden-high (TMB-H) greater than 10 mutations/megabase, as determined by an FDA-approved test, who have progressed following prior treatment and who have no satisfactory alternative treatment options.

The FDA has set a Prescription Drug User Fee Act (PDUFA), or target action, date of June 16, 2020.

“From the start, biomarker research has been a critical aspect of our clinical program evaluating Keytruda monotherapy,” said Dr. Scot Ebbinghaus, vice president, clinical research, Merck Research Laboratories. “TMB has been an area of scientific interest to help identify patients most likely to benefit from Keytruda.

The application was based in part on results from the Phase II KEYNOTE-158 trial, which also supported Merck’s 2017 FDA approval for Keytruda as the first cancer treatment based on a biomarker, regardless of cancer type, in microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) solid tumors. MSI-H is on the highest end of the TMB spectrum. Data from KEYNOTE-158 on the TMB-H patient population were presented at the European Society for Medical Oncology (ESMO) 2019 Congress.

“Tissue tumor mutational burden-high,” or TMB-H, are tumors with at least 10 mutations per megabase or greater, which would be determined via an FDA-approved test. Merck Inc., is relying on evidence from the same Keynote-158 study that led to its first tissue-agnostic approval in 2017. Updated evidence from the study last year showed higher response rates to Keytruda for people with TMB-high tumors than others..