Keytruda's Original FDA Approval
Keytruda (pembrolizumab) received its first U.S. FDA approval on September 4, 2014, for unresectable or metastatic melanoma in patients whose tumors express PD-L1, as determined by an FDA-approved test.[1][2]
How the Approval Happened
The approval stemmed from the KEYNOTE-001 trial, a phase 1 study showing 33% objective response rate and 4-month median duration in PD-L1-positive advanced melanoma patients.[1][3] This marked the first PD-1 inhibitor approval, based on accelerated pathways for breakthrough therapies.
Expansion to Other Cancers
Keytruda quickly gained approvals beyond melanoma:
- December 2014: Ipilimumab-refractory melanoma.
- October 2015: Non-small cell lung cancer (NSCLC) expressing PD-L1.
By 2024, it has 40+ indications across 18 tumor types, including MSI-H cancers regardless of location.[1][4]
Why Melanoma First?
Melanoma's high unmet need and PD-1 pathway's role in immune evasion made it the lead; early trials prioritized immunotherapy-resistant cases.[3][5]
Current Status and Patents
Keytruda remains Merck's top seller at $25B+ annual revenue. U.S. composition-of-matter patent expires in 2028, with challenges ongoing; pediatric exclusivity adds six months.[6][1]
[1]: FDA Approval History
[2]: Keytruda Prescribing Information
[3]: NEJM KEYNOTE-001 Results
[4]: Merck Keytruda Indications
[5]: ASCO Post on PD-1 History
[6]: DrugPatentWatch.com - Keytruda Patents