MERCK SHARP DOHME — Keytruda FDA Review (NDA/BLA 125514, 2023)
Merck & Co., Inc. · 2023 · FDA Review (Drugs@FDA) · company profile →
Report summary
The FDA approved Merck Sharp & Dohme's KEYTRUDA (pembrolizumab) on July 30, 2019, for numerous cancer indications, including melanoma, NSCLC, SCLC, HNSCC, cHL, PMBCL, urothelial carcinoma, MSI-H cancer, gastric cancer, esophageal cancer, cervical cancer, hepatocellular carcinoma, Merkel cell carcinoma, and renal cell carcinoma. Many approvals were accelerated, contingent on confirmatory trials. The approval package details Keytruda's comprehensive safety profile across various trials, highlighting immune-mediated adverse reactions, infusion-related reactions, and HSCT complications. Adverse event rates, including those leading to discontinuation, are provided for Keytruda as a single agent and in combination with chemotherapy, often compared to active comparators. Efficacy data, including overall survival (OS), progression-free survival (PFS), and objective response rates (ORR), are presented for various cancer types and treatment lines. Specifically, for esophageal squamous cell carcinoma (ESCC) with PD-L1 CPS ≥10, the FDA granted traditional approval based on KEYNOTE-181 and KEYNOTE-180 trials, which demonstrated clinically meaningful improvements in OS, PFS, and ORR, with a favorable safety profile compared to chemotherapy.
Key findings — cited to the page
| Most frequently reported Grade 3 to 5 drug-related AEs (chemotherapy arm) - neutrophil count decreased | 9.8 % | KEYNOTE-181 · p.197 |
| Laboratory abnormalities with clinically meaningful (Grade 3 to 4 events) worsening from baseline (neutrophils decreased, SOC arm) | 22.2 % | KEYNOTE-181 · p.203 |
| Most frequently reported Grade 3 to 5 AEs related to pembrolizumab (autoimmune hepatitis) | 1.6 % | KEYNOTE-181 · p.197 |
| Most frequently reported Grade 3 to 5 drug-related AEs (chemotherapy arm) - white blood cell count decreased | 10.1 % | KEYNOTE-181 · p.197 |
| Laboratory abnormalities with clinically meaningful (Grade 3 to 4 events) worsening from baseline (leukocytes decreased, SOC arm) | 24.3 % | KEYNOTE-181 · p.203 |
| Laboratory abnormalities with clinically meaningful (Grade 3 to 4 events) worsening from baseline (neutrophils decreased, pembrolizumab arm) | 1.1 % | KEYNOTE-181 · p.203 |
| Grade 3-5 treatment-emergent adverse events (chemotherapy arm) | 62 % | KEYNOTE-181 · p.197 |
| Grade 3-5 treatment-emergent adverse events (pembrolizumab arm) | 54 % | KEYNOTE-181 · p.197 |
| Most frequently reported Grade 3 to 5 AEs related to pembrolizumab (asthenia) | 1.3 % | KEYNOTE-181 · p.197 |
| Most frequently reported Grade 3 to 5 AEs related to pembrolizumab (anemia) | 1.3 % | KEYNOTE-181 · p.197 |
| Laboratory abnormalities with clinically meaningful (Grade 3 to 4 events) worsening from baseline (leukocytes decreased, pembrolizumab arm) | 0.7 % | KEYNOTE-181 · p.203 |
| Grade 1 pneumonitis (esophageal cancer dataset) | 3 | · p.205 |
Source: Merck & Co., Inc. ↗ · License: US Government public domain. Summary and findings are extracted from the published document; every figure cites its page. Informational only — not investment advice. Explore the Oncology library →