In the multicohort, phase 1B KEYNOTE-001 study, the anti–PD-1 antibody pembro provided a 19.4% ORR in 495 pts with previously treated or treatment-naive NSCLC; ORR was 45.2% in pts with membranous PD-L1 expression in ≥50% of tumor cells (tumor proportion score [TPS] ≥50%). We present data for the 22 pts with previously treated NSCLC from Korea enrolled in KEYNOTE-001.
Pts received pembro 10 mg/kg Q3W (n = 14) or 10 mg/kg Q2W (n = 8) until confirmed progression, intolerable toxicity, or investigator decision. Response was assessed every 9 wk per RECIST v1.1 by central review. PD-L1 expression in tumors was assessed by immunohistochemistry using a clinical trial assay. Pts were evaluable for PD-L1 only if tumor slides were prepared within 6 mo of staining and a PD-L1 TPS could be assigned.
Median age was 60.5 y (range 41-80), 77.3% of pts were men, 77.3% were former smokers, 63.6% had nonsquamous histology, and 18.2% had EGFR mutation. All pts received ≥1 prior therapy, including 31.8% who received ≥4 prior therapies. Nine (40.9%) pts experienced ≥1 treatment-related AE, only 1 of whom experienced events of grade ≥3 severity (grade 4 cardiac tamponade and grade 3 elevated ALT and bilirubin). One case of pneumonitis (grade 2 severity) was reported. No pts experienced treatment-related death or discontinued for a treatment-related AE. ORR was 27.3% overall and 75.0% in pts with TPS ≥50% (Table). At data cutoff, 4 of 6 (66.7%) responders were alive, progression free, and without new anticancer treatment; median duration of response was not reached (NR) (range 2.3+ to 6.6+ mo). Median PFS was 4.2 mo (95% CI 2.0-NR), and the 6-mo PFS rate was 40.9%. The 6-mo OS rate was 77.3%; median OS was NR (95% CI 7.0 mo-NR).
Antitumor Activity by PD-L1 TPS (*includes 11 pts for whom a PD-L1 TPS could not be assigned)
|End Point||Total N = 22*||PD-L1 TPS ≥50% n = 4||PD-L1 TPS 1-49% n = 5||PD-L1 TPS <1% n = 2|
|ORR, % (95% CI)||27.3 (10.7-50.2)||75.0 (19.4-99.4)||20.0 (0.5-71.6)||0.0 (0.0-84.2)|
|DCR, % (95% CI)||68.2 (45.1-86.1)||75.0 (19.4-99.4)||60.0 (14.7-94.7)||100.0 (15.8-100.0)|
As was found in the overall KEYNOTE-001 NSCLC population, pembro has a manageable safety profile and provides robust, durable antitumor activity in pts from Korea with previously treated NSCLC, particularly those with PD-L1 TPS ≥50%.
Clinical trial identification
B. Piperdi: current employee of Merck & Co., Inc. Owns stock in Merck & Co., Inc. J. Zhang, G.M. Lubiniecki: employee of Merck & Co., Inc. M.-J. Ahn: Advisory board member for AstraZeneca, Eli Lilly, and Boehringer Ingelheim. All other authors have declared no conflicts of interest.