On October 16, 2026, the U.S. Food and Drug Administration (FDA) granted traditional approval to pembrolizumab (Keytruda) or pembrolizumab and berahyaluronidase alfa-pmph (Keytruda Qlex) for the treatment of 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 an accelerated approval for the treatment of adult and pediatric patients with unresectable or metastatic TMB-H, solid tumors, where TMB-H was defined as ≥ 10 mut/Mb. 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 for patients with a tumor mutational burden of 10 to < 13 mut/Mb.
Efficacy and Safety
Efficacy was evaluated in two groups of patients, the first being Cohort M of the KEYNOTE-158 trial (ClinicalTrials.gov identifier NCT02628067), which prospectively enrolled patients with tumors that were TMB-H and not microsatellite instability-high (MSI-H). Cohorts A through J comprised a prospectively planned retrospective analysis of patients with TMB-H tumors identified within 10 cohorts of patients with various previously treated unresectable or metastatic solid tumors. Patients in Cohorts A through J received pembrolizumab 200 mg every 3 weeks and patients in Cohort M received pembrolizumab 400 mg intravenously every 6 weeks until unacceptable toxicity or documented disease progression.
The major efficacy outcome measures were objective response rate and duration of response in 220 patients with tumors with TMB ≥ 13 mut/Mb (145 in Cohort M and 75 in Cohorts A–J) who received at least one dose of pembrolizumab, as assessed by blinded independent central review according to RECIST v1.1, modified to follow a maximum of 10 target lesions and a maximum of 5 target lesions per organ. Across both groups, the objective response rate was 36% (95% confidence interval = 30%–43%) and 58% of patients had a duration of response lasting at least 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 3 weeks or 400 mg every 6 weeks until disease progression, unacceptable toxicity, or up to 24 months. The recommended dose for pediatric patients is 2 mg/kg every 3 weeks (up to a maximum of 200 mg) until disease progression, unacceptable toxicity, or up to 24 months.
This review used the Assessment Aid, a voluntary applicant submission to facilitate the FDA’s assessment.
