FDA grants traditional approval for pembrolizumab or pembrolizumab and berahyaluronidase alfa-pmph for unresectable or metastatic TMB-H solid tumors with updated indication
Regulatory approval news: The FDA has granted traditional approval for pembrolizumab (Keytruda) or pembrolizumab plus berahyaluronidase alfa-pmph (Keytruda QLEX) for adult and pediatric patients with unresectable or metastatic tumor mutational burden–high (TMB-H) solid tumors (≥13 mut/Mb by an FDA-authorized test) that progressed after prior treatment and have no satisfactory alternatives. The action converts a prior accelerated approval and updates the TMB-H cutoff from ≥10 to ≥13 mut/Mb based on evidence from KEYNOTE-158.
FDA converts pembrolizumab TMB-H indication to traditional approval and raises cutoff to ≥13 mut/Mb
Type: Regulatory approval (FDA)
The FDA granted traditional approval for pembrolizumab (Keytruda) or pembrolizumab and berahyaluronidase alfa-pmph (Keytruda QLEX) for adult and pediatric patients with unresectable or metastatic TMB-H solid tumors defined as ≥13 mutations/megabase, as determined by an FDA-authorized test, whose disease has progressed following prior treatment and who have no satisfactory alternative treatment options.
This action converts the previous accelerated approval for TMB-H solid tumors (previously ≥10 mut/Mb) to traditional approval and amends the biomarker definition. The FDA stated that efficacy supporting traditional approval was not confirmed in patients with TMB 10 to <13 mut/Mb.
Evidence base (KEYNOTE-158; NCT02628067)
Efficacy was evaluated in 220 patients with TMB ≥13 mut/Mb (145 in Cohort M; 75 in Cohorts A–J) receiving pembrolizumab, assessed by BICR per RECIST v1.1 (modified). Across groups, ORR was 36% (95% CI, 30–43), and 58% of responders had DOR ≥12 months.
Safety and dosing
Safety was reported as consistent with known pembrolizumab monotherapy safety, with labeled warnings including immune-mediated adverse reactions, infusion-related reactions, allogeneic HSCT complications, and embryo-fetal toxicity. Recommended adult dosing: 200 mg q3w or 400 mg q6w (up to 24 months); pediatric: 2 mg/kg q3w (max 200 mg; up to 24 months).