FDA gives Keytruda full approval for TMB-high solid tumours but raises the eligibility threshold

The US Food and Drug Administration has converted the accelerated approval of Merck’s Keytruda (pembrolizumab), and its under-the-skin version Keytruda Qlex, for tumour mutational burden-high (TMB-H) solid tumours into a traditional (full) approval — but for a narrower group. The decision is dated 16 October 2026; the FDA posted it on 22 October.

What changed

• The indication covers adults and children with unresectable or metastatic TMB-H solid tumours that have progressed after prior treatment and who have no satisfactory alternative options.
• TMB-H is now defined as at least 13 mutations per megabase (mut/Mb), measured by an FDA-authorised test. The 2020 accelerated approval used a cut-off of 10 mut/Mb.
• The FDA says efficacy to support full approval was not confirmed in patients whose tumours had a TMB of 10 to under 13 mut/Mb.

The evidence

Efficacy came from 220 patients with TMB of at least 13 mut/Mb in the KEYNOTE-158 trial: 145 enrolled prospectively in Cohort M and 75 identified in a planned retrospective analysis of Cohorts A–J. The objective response rate was 36%, and 58% of responders kept their response for at least 12 months.

Limitations

KEYNOTE-158 is a single-arm study with no control group, and the main outcomes were tumour response and its duration rather than overall survival. Part of the data comes from a retrospective analysis. Patients whose tumours fall between 10 and 13 mut/Mb are no longer covered by the label. As GenomeWeb notes, the move tightens a biomarker used to pick patients for a tumour-agnostic therapy. Patients should discuss testing and treatment with their oncologist.