On June 16, 2020, the FDA granted accelerated approval to pembrolizumab (Keytruda; Merck) 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 that progressed after prior therapy, have no satisfactory alternative treatment options, and which were determined via an FDA-approved test. The application for this approval was given priority review by the FDA.

In addition, the FDA approved a companion diagnostic for pembrolizumab on this date, the FoundationOneCDx assay (Foundation Medicine).

The approval of pembrolizumab for this indication was based on efficacy data from a retrospective analysis of 10 patient cohorts comprising patients with pre-treated, unresectable or metastatic TMB-H solid tumors enrolled in the multi-center, nonrandomized KEYNOTE-158 trial.

Patients in the open-label study were given pembrolizumab 200 mg every 3 weeks until unacceptable toxicity or disease progression occurred.

The main efficacy end points were overall response rate and response duration in patients who received at least 1 dose pembrolizumab dose, as assessed by blinded independent central review.

Overall, 102 (13%) patients had TMB-H tumors. These patients had an overall response rate of 29% (95% CI, 21-39), including 4% complete and 25% partial response rates.

While the median duration of response was not reached, 57% of patients had responses lasting ≥12 months and 50% had responses for ≥24 months.

Notably, patients with TMB-H cancer in the KEYNOTE-158 trial had adverse events similar to those occurring in patients with other solid tumors given pembrolizumab monotherapy.

Fatigue, musculoskeletal pain, decreased appetite, pruritus, diarrhea, nausea, rash, pyrexia, cough, dyspnea, constipation, pain, and abdominal pain are the adverse events most frequently associated with pembrolizumab use.—Hina M. Porcelli

Source: US Food and Drug Administration. FDA approves pembrolizumab for adults and children with TMB-H solid tumors. Updated June 17, 2020. www.fda.gov/drugs/drug-approvals-and-databases/fda-approves-pembrolizumab-adults-and-children-tmb-h-solid-tumors. Accessed June 17, 2020.