KEYNOTE-001 — Phase 1 Study of Pembrolizumab (MK-3475) in Patients With Advanced Melanoma and Non-Small Cell Lung Cancer

Phase 1 · 2015 · Melanoma, Non-Small Cell Lung Cancer

Design

Large multi-cohort phase 1 trial with dose-finding and disease-specific expansion cohorts; retrospectively defined and validated the PD-L1 tumor proportion score (TPS) cutoffs.

Population

Advanced melanoma and advanced NSCLC, treatment-naive and previously treated.

Primary Endpoint

safety, tolerability, and antitumor activity (ORR)

Key Result

5-year OS ~34% in advanced melanoma (41% in treatment-naive) and ~23% in NSCLC (with the highest survival in PD-L1 TPS >=50%); responses were highly durable.

Guideline Impact

Basis for pembrolizumab's initial accelerated approval in melanoma and for PD-L1-guided patient selection