FDA grants traditional approval for pembrolizumab in TMB-high tumors

The FDA granted traditional approval on October 16, 2026, to pembrolizumab (Keytruda) or pembrolizumab with berahyaluronidase alfa-pmph (Keytruda Qlex) for adults and children with unresectable or metastatic TMB-high solid tumors. Patients must have disease that progressed after prior treatment, no satisfactory alternative treatment options, and a tumor result from an FDA-authorized test. The updated indication defines TMB-high as ≥13 mutations/megabase (mut/Mb), replacing the prior threshold of ≥10 mut/Mb. The FDA said efficacy supporting traditional approval was not confirmed in patients with TMB of 10 to <13 mut/Mb.

In the efficacy analysis, 220 patients with tumors at ≥13 mut/Mb received pembrolizumab. The objective response rate was 36%, and 58% of patients had a response lasting ≥12 months. The FDA said the safety profile was consistent with the known profile of pembrolizumab monotherapy. Prescribing information includes warnings for immune-mediated adverse reactions, infusion-related reactions, complications of allogeneic hematopoietic stem cell transplantation, and embryo-fetal toxicity.