Optimizing PD-L1 as a biomarker of response with pembrolizumab (pembro; MK-3475) as first-line therapy for PD-L1–positive metastatic non-small cell lung cancer (NSCLC): Updated data from KEYNOTE-001.

8026 Background: Platinum doublets provide 6-mo PFS and 12-mo OS for treatment-naive, metastatic NSCLC without driver mutations. Preliminary data from KEYNOTE-001 revealed robust antitumor activity and manageable toxicity for the anti–PD-1 antibody pembro in treatment-naive NSCLC. In these patients (pts), PD-L1 positivity correlated with improved ORR, PFS, and OS. We explored the relationship between PD-L1 expression levels and efficacy in treatment-naive pts in KEYNOTE-001. Methods: 101 treatment-naive, PD-L1+ metastatic NSCLC pts were randomized 1:1 to pembro 10 mg/kg Q2W or Q3W (11 pts randomized to 2 or 10 mg/kg Q3W). Pembro was given until unacceptable toxicity, PD, or pt/investigator decision. PD-L1 expression was assessed by IHC (22C3 antibody). Staining of tumor cells or stroma by a prototype assay was used for enrollment. In a prospectively defined validation set (n = 90), the percentage of PD-L1–stained tumor cells was determined with a clinical trial assay. Response was assessed centrally every...