![]() 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. 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. 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. 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). Healthcare professionals should report all serious adverse events suspected to be associated with the use of any medicine and device to FDA’s MedWatch Reporting System or by calling 1-80.The FDA approved pembrolizumab on June 16, 2020, for the treatment of adult and pediatric patients with unresectable or metastatic tumor mutational burden–high solid tumors, as determined by an FDA-approved test, that have progressed following prior treatment and who have no satisfactory alternative treatment options. A description of FDA expedited programs is in the Guidance for Industry: Expedited Programs for Serious Conditions-Drugs and Biologics. This application was granted priority review. This review used the Assessment Aid, a voluntary submission from the applicant to facilitate the FDA’s assessment. View full prescribing information for KEYTRUDA. The recommended pembrolizumab dosage regimen for TMB-H solid tumors is 200 mg every 3 weeks or 400 mg every 6 weeks for adults 2 mg/kg (up to a maximum of 200 mg) every 3 weeks for pediatric patients. The prescribing information for pembrolizumab includes a “Limitation of Use” stating that the safety and effectiveness of pembrolizumab in pediatric patients with TMB-H central nervous system cancers have not been established. Pembrolizumab is associated with immune-mediated side effects, including pneumonitis, colitis, hepatitis, endocrinopathies, nephritis, and skin adverse reactions. The most common adverse reactions to pembrolizumab are fatigue, musculoskeletal pain, decreased appetite, pruritus, diarrhea, nausea, rash, pyrexia, cough, dyspnea, constipation, pain, and abdominal pain. The median DoR was not reached, with 57% of patients having response durations ≥12 months and 50% of patients having response durations ≥24 months.Īdverse reactions occurring in patients with TMB‑H cancer enrolled in KEYNOTE-158 were similar to those occurring in patients with other solid tumors who received pembrolizumab as a single agent. The ORR for these patients was 29% (95% CI: 21,39), with a 4% complete response rate and 25% partial response rate. The main efficacy outcome measures were overall response rate (ORR) and duration of response (DoR) in patients who have received at least one dose of pembrolizumab as assessed by blinded independent central review according to RECIST v1.1, modified to follow a maximum of 10 target lesions and a maximum of 5 target lesions per organ.Ī total of 102 patients (13%) had tumors identified as TMB-H, defined as TMB ≥10 mut/Mb. Patients received pembrolizumab 200 mg intravenously every 3 weeks until unacceptable toxicity or documented disease progression. Today, the FDA also approved the FoundationOneCDx assay (Foundation Medicine, Inc.) as a companion diagnostic for pembrolizumab.Įfficacy was investigated in a prospectively-planned retrospective analysis of 10 cohorts of patients with various previously treated unresectable or metastatic TMB-H solid tumors enrolled in a multicenter, non-randomized, open-label trial, KEYNOTE-158 (NCT02628067). On June 16, 2020, the Food and Drug Administration granted accelerated approval to pembrolizumab (KEYTRUDA, Merck & Co., Inc.) for the treatment of adult and pediatric patients with unresectable or metastatic tumor mutational burden-high (TMB-H) solid tumors, as determined by an FDA-approved test, that have progressed following prior treatment and who have no satisfactory alternative treatment options.
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