MERCK SHARP DOHME — Keytruda FDA Review (NDA/BLA 125514, 2023)
Merck & Co., Inc. · 2023 · FDA Review (Drugs@FDA) · company profile →
Report summary
Keytruda (pembrolizumab) received FDA approval on September 17, 2019, for numerous cancer indications, including melanoma, NSCLC, SCLC, HNSCC, cHL, PMBCL, urothelial carcinoma, MSI-H cancer, gastric cancer, esophageal cancer, cervical cancer, HCC, MCC, RCC, and endometrial carcinoma. Many approvals, especially for advanced endometrial carcinoma in combination with lenvatinib, were accelerated based on response rates, requiring confirmatory trials. The drug's detailed dosage and administration guidelines are provided, alongside warnings for immune-mediated adverse reactions like pneumonitis, colitis, hepatitis, endocrinopathies, nephritis, and skin reactions. Safety data from multiple clinical trials confirm these adverse events, with incidence rates, onset times, and durations documented for both monotherapy and combination regimens. Efficacy results demonstrate Keytruda's superiority in overall and progression-free survival across various cancers, often compared to standard treatments or placebo. The combination of lenvatinib and pembrolizumab for advanced endometrial carcinoma, particularly in non-MSI-H/dMMR patients, showed significant objective response rates and duration of response, leading to accelerated approval. While combination therapy increased adverse event rates, no new safety signals were identified. The FDA's review included extensive analysis of efficacy, safety, and labeling, with ongoing post-marketing commitments.
Key findings — cited to the page
| Grade ≥3 hepatotoxicity (excluding elevated LFTs) | 7 % | · p.182 |
| Worst CTCAE Grade 2 for Lenvatinib | 28.2 % | Lenv Monotx 24mg (N=1119) · p.232 |
| ORR (CR + PR) for FIGO Grade 3 EC | 42.0 % | Study 111 · p.159 |
| Grade ≥3 hypertension | 39 % | · p.182 |
| Grade ≥3 palmar-plantar erythrodysesthesia | 3.2 % | · p.182 |
| Grade ≥3 renal events | 3.2 % | · p.182 |
| ORR (CR + PR) for FIGO Grade 1 EC | 40.0 % | Study 111 · p.159 |
| ORR (CR + PR) for FIGO Grade 2 EC | 20.0 % | Study 111 · p.159 |
| Permanent discontinuation due to adverse reaction (Grade 1-4) | 17 % | · p.181 |
| Grade ≥3 CSEs | 46 events | · p.182 |
| Grade ≥3 hemorrhages | 3.2 % | · p.182 |
| TEAEs leading to lenvatinib dose interruptions (Grade 1-5) | 65 % | not-MSI-H/dMMR EC 2L+ group · p.230 |
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 →