FDA grants traditional approval for pembrolizumab or pembrolizumab and berahyaluronidase alfa-pmph for unresectable or metastatic TMB-H solid tumors with updated indication

On October 16, 2026, the Food and Drug Administration granted traditional approval to pembrolizumab (Keytruda, Merck) or pembrolizumab and berahyaluronidase alfa-pmph (Keytruda Qlex, Merck) for adult and pediatric patients with unresectable or metastatic tumor mutational burden-high (TMB-H) [≥13 mutations/megabase (mut/Mb)] solid tumors, as determined by an FDA-authorized test, that have progressed following prior treatment and who have no satisfactory alternative treatment options.

Previously, pembrolizumab received accelerated approval for the treatment of adult and pediatric patients with unresectable or metastatic TMB-H, defined as ≥10 mutations/megabase (mut/Mb), solid tumors. This approval converts the accelerated approval to traditional approval and amends the TMB-H indication to define TMB-H as ≥13 mut/Mb, as efficacy to support traditional approval was not confirmed in patients with TMB of 10 to <13 mut/Mb.

Efficacy and Safety

Efficacy was evaluated in two groups of patients in KEYNOTE-158 (NCT02628067): Cohort M prospectively enrolled patients with tumors that were TMB-H and not microsatellite instability-high (MSI-H) and Cohorts A through J consisted of a prospectively planned retrospective analysis of patients with TMB-H tumors identified within 10 cohorts (A through J) of patients with various previously treated unresectable or metastatic solid tumors. Patients in Cohorts A-J received pembrolizumab 200 mg every three weeks and patients in Cohort M received pembrolizumab 400 mg intravenously every six weeks until unacceptable toxicity or documented disease progression.

The major efficacy outcome measures were objective response rate (ORR) and duration of response (DOR) in 220 patients with tumors with TMB ≥13 mut/Mb (145 in Cohort M and 75 in Cohorts A to J) who received at least one dose of pembrolizumab as assessed by BICR according to RECIST v1.1, modified to follow a maximum of 10 target lesions and a maximum of five target lesions per organ. Across both groups, ORR was 36% (95% CI: 30, 43) and 58% of patients had a DOR of ≥12 months.

The safety profile of pembrolizumab monotherapy for the updated indication was consistent with the known safety profile of pembrolizumab monotherapy.

The prescribing information includes warnings and precautions for immune-mediated adverse reactions, infusion-related reactions, complications of allogeneic hematopoietic stem cell transplantation, and embryo-fetal toxicity.

Recommended Dosage

The recommended dose of pembrolizumab monotherapy for the updated indication is 200 mg every three weeks or 400 mg every six weeks until disease progression, unacceptable toxicity, or up to 24 months. The recommended dose for pediatric patients is 2 mg/kg every three weeks (up to a maximum of 200 mg) until disease progression, unacceptable toxicity, or up to 24 months. For dosage and administration information for pembrolizumab and berahyaluronidase alfa-pmph refer to its prescribing information.

Full prescribing information for Keytruda and Keytruda QLEX will be posted on Drugs@FDA.

This review used the Assessment Aid, a voluntary submission from the applicant to facilitate the FDA’s assessment.

Healthcare professionals should report all serious adverse events suspected to be associated with the use of any medicine and device to FDA’s MedWatch Reporting System or by calling 1-800-FDA-1088.

For assistance with single-patient INDs for investigational oncology products, healthcare professionals may contact OCE’s Project Facilitate at 240-402-0004 or email OncProjectFacilitate@fda.hhs.gov