FDA raises TMB threshold for pembrolizumab

Traditional approval narrows eligibility for previously treated solid tumors after efficacy was not confirmed at lower biomarker levels.

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The FDA raised the TMB threshold for pembrolizumab and pembrolizumab/berahyaluronidase alfa-pmph from 10 to 13 mutations per megabase.
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The traditional approval covers adults and pediatric patients with unresectable or metastatic TMB-high solid tumors that progressed after prior treatment and have no satisfactory alternatives.
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TMB status must be determined with an FDA-authorized test, and efficacy was not confirmed in patients with TMB levels of 10 to less than 13 mutations per megabase.
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In KEYNOTE-158, the efficacy population included 220 patients with TMB levels of at least 13 mutations per megabase, and there was no randomized comparator.
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Across the trial groups, the objective response rate was 36%, and 58% of responders maintained their response for at least 12 months.

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