On October 2, 2015, the U. S. Food and Drug Administration granted accelerated approval to pembrolizumab (KEYTRUDA Injection, Merck Sharp and Dohme Corporation) for the treatment of patients with metastatic non-small cell lung cancer (NSCLC) whose tumors express programmed death ligand 1 (PD-L1) as determined by an FDA-approved test, with disease progression on or after platinum-containing chemotherapy. Patients with EGFR or ALK genomic tumor aberrations should have disease progression on FDA-approved therapy for these aberrations prior to receiving pembrolizumab.
Approval was based on demonstration of a durable objective response rate (ORR) in an international, multicenter, open-label, activity-estimating subgroup within Trial P001. This prospectively identified and retrospectively analyzed subgroup included 61 patients with NSCLC, PD-L1 expression tumor proportion score (TPS) of greater than or equal to 50% tumor cells, and disease progression on or after platinum-containing chemotherapy, and, if appropriate, targeted therapy for ALK or EGFR mutations. Patients received intravenous pembrolizumab 10 mg/kg every 3 weeks or every 2 weeks.
ORR was determined by blinded independent review committee according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. The ORR for the 61 patients was 41.0% [95% confidence interval (CI): 28.6%, 54.3%)]. The median response duration was not yet reached at the analysis time. Of the 25 patients with responses, 21 (84%) remained without disease progression, and 11 patients had responses for at least 6 months.
Safety data was evaluated in 550 patients with NSCLC receiving at least one dose of pembrolizumab 10 mg/kg every 2 or every 3 weeks, or 2 mg/kg every 3 weeks. The most common (greater than or equal to 20%) adverse reactions included fatigue, decreased appetite, dyspnea and cough. The most frequent (greater than or equal to 2%) serious adverse drug reactions were pleural effusion, pneumonia, dyspnea, pulmonary embolism, and pneumonitis. Clinically significant immune-mediated adverse reactions included pneumonitis, colitis, hypophysitis, and thyroid disorders.
As a condition of this accelerated approval, Merck is required to conduct a multicenter, randomized trial establishing the superiority of pembrolizumab over standard therapy to verify and describe the clinical benefit of pembrolizumab. Merck has an ongoing multicenter, randomized trial in patients with NSCLC (Trial P010) with co-primary endpoints of progression-free survival and overall survival.
An FDA approved companion diagnostic, PD-L1 IHC 22C3 pharmDx, to determine PD-L1 expression is now available.
The recommended dose and schedule of pembrolizumab is 2 mg/kg administered as an intravenous infusion over 30 minutes every 3 weeks.
Full prescribing information, including clinical trial information, safety, dosing, drug-drug interactions and contraindications is available at: http://www.accessdata.fda.gov/drugsatfda_docs/label/2015/125514s005lbl.pdf.
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 by completing a form online at http://www.fda.gov/medwatch/report.htm, by faxing (1-800-FDA-0178) or mailing the postage-paid address form provided online, or by telephone (1-800-FDA-1088).