Keytruda gets the full green light for hard-to-treat solid tumors. The FDA has converted pembrolizumab's accelerated approval to full (traditional) approval for unresectable or metastatic tumor mutational burden–high (TMB-H) solid tumors — but with a catch: the qualifying TMB threshold has been raised from 10 to 13 mutations per megabase. The decision was backed by a 36% overall response rate in the phase 2 KEYNOTE-158 trial.
Keytruda earns full FDA approval for TMB-H solid tumors — but the bar just got higher
The FDA has granted traditional (full) approval to pembrolizumab (Keytruda) — and its subcutaneous formulation with berahyaluronidase alfa-pmph (Keytruda Qlex) — for adult and pediatric patients with unresectable or metastatic TMB-H solid tumors who have progressed on prior treatment and have no satisfactory alternatives. This converts the accelerated approval first granted in June 2020.
The key update: the TMB-H threshold has been raised from ≥10 to ≥13 mutations per megabase (mut/Mb). Efficacy data generated since 2020 did not support full approval for patients in the 10–12 mut/Mb range, effectively narrowing the eligible population. The approval was supported by data from the phase 2 KEYNOTE-158 trial, an open-label, nonrandomized study across multiple advanced solid tumor types (excluding melanoma and NSCLC).
By the Numbers
Why it matters: Full approval signals stronger confidence in pembrolizumab's benefit for this biomarker-selected population — but clinicians should note the updated, stricter TMB cutoff when identifying eligible patients.
