FDA Approves Second Biomarker-Specific Indication for Merck’s Keytruda

Merck’s vaunted checkpoint inhibitor Keytruda won approval for a new indication. The anti-PD-1 therapy was approved as a monotherapy for the treatment of adult and pediatric patients with unresectable or metastatic tumor mutational burden-high (TMB-H) solid tumors determined through biomarker-based testing.

This is the second such biomarker-specific approval for Keytruda. The first biomarker-specific approval came in 2017. Keytruda was approved for adult and pediatric patients with solid tumors identified with a biomarker called microsatellite instability-high or mismatch repair deficient.

On Tuesday, the U.S. Food and Drug Administration (FDA) gave the green light to Keytruda for this indication in patients whose disease has progressed following prior treatment and who have no satisfactory alternative treatment options. The latest nod for Keytruda was made under accelerated approval based on tumor response rate and durability of response. This latest approval marks Keytruda as the first checkpoint inhibitor approved for these patients who have TMB-H solid tumors, Merck said.

The approval was based on data from an analysis of 10 cohorts of patients who have various previously treated unresectable or metastatic solid tumors with TMB-H and had been enrolled in the KEYNOTE-158 study. The trial excluded patients who previously received an anti-PD-1 or other immune-modulating monoclonal antibody, or who had an autoimmune disease, or a medical condition that required immunosuppression. TMB status was assessed using the FoundationOne CDx assay, which also received FDA approval as a companion diagnostic. The major efficacy outcome measures were objective response rate and duration of response in the patients who received at least one dose of Keytruda, Merck said. In the patients whose tumors were TMB-H, Keytruda demonstrated an ORR of 29%, with a complete response rate of 4% and a partial response rate of 25%. The median duration of response was not reached, with 57% of patients having response durations greater than months and 50% of patients having response durations of more than two years, the FDA said in its announcement.

Scott Ebbinghaus, vice president of clinical research at Merck Research Laboratories, touted the importance of the latest approval based on a biomarker rather than the location in the body where the tumor originated.

“TMB-H, defined as 10 mutations per megabase or more, can help identify patients most likely to benefit from Keytruda. We’re pleased that our collaborative efforts to advance biomarker research have resulted in our ability to provide a new treatment option that addresses a high unmet medical need for these patients with cancer,” Ebbinghaus said in a statement.

Speaking about the FDA approval of its companion diagnostic piece, Foundation Medicine Chief Medical Officer Brian Alexander said it is critical that healthcare professionals have access to a validated genomic test to measure TMB in clinical tumor assessments and pinpoint those who are more likely to respond.