FDA Approval Summary: Pembrolizumab for the Treatment of Tumor Mutational Burden–High Solid Tumors

Abstract The FDA approved pembrolizumab on June 16, 2020, for the treatment of adult and pediatric patients with unresectable or metastatic tumor mutational burden–high [TMB-H; ≥10 mutations/megabase (mut/Mb)] solid tumors, as determined by an FDA-approved test, that have progressed following prior treatment and who have no satisfactory alternative treatment options. FDA granted the approval based on a clinically important overall response rate (29%; 95% confidence interval, 21–39) and duration of response (57% of responses lasting ≥ 12 months) in the subset of patients with TMB-H solid tumors (n = 102) spanning nine different tumor types enrolled in a multicenter single-arm trial (KEYNOTE-158). The efficacy of pembrolizumab was supported by the results of whole-exome sequencing (WES) analyses of TMB in additional patients enrolled across multiple pembrolizumab clinical trials, and a scientific understanding of the effects of PD-1 inhibition. Overall, the adverse event profile of pembrolizumab was similar to the adverse event profile observed in prior trials that supported the approval of pembrolizumab in other indications. This approval of pembrolizumab is the first time that the FDA has approved a cancer treatment for an indication based on TMB, and the fourth based on the presence of a biomarker rather than the primary site of origin.