Primary results from Japanese phase I study of pembrolizumab plus chemotherapy as front-line therapy for advanced NSCLC

Abstract

Background: The anti PD 1 antibody pembrolizumab (pembro) exhibits robust antitumor activity in patients with advanced NSCLC. In part BC of KEYNOTE 011 (NCT01905657), we evaluated the efficacy and safety of pembro+ chemotherapy combinations in advanced NSCLC. Here we report primary results from both studies. This is the longest follow-up data on treatment of pembro plus standard chemotherapy regimens in JapaneseNSCLC patients. Methods: Chemotherapy-naive, advanced, EGFR/ALK NSCLC pts, PS 0 or 1, were treated to pembro plus either cisplatin or carboplatin + pemetrexed (PEM) (part B, non-squamous), or carboplatin and paclitaxel or nab-paclitaxel (part C, squamous) for 4 cycles followed by maintenance pembro + PEM (B), pembro (C). Results: In part B, 12 pts (6 in cisplatin cohort, 6 in carboplatin cohort) had been treated; median (range) follow-up duration was 16.0 mo (3.7 21.2 mo). 1 DLT occurred in cisplatin cohort (Grade 4 Hyponatremia) during the DLT evaluation period. At the time of data cutoff, ≥Gr 3 treatment-related AEs occurred in 75.0%, 2 treatmentrelated death occurred (2 pneumonitis in carboplatin cohort). ORR was 66.7% and 80.0% in cisplatin and carboplatin cohort, respectively. ORR with cohorts combined in TPS ≥50%, TPS = 149%, TPS < 1% were 100%, 66.7%, and 66.7%, respectively. In part C, 14 pts (8 in paclitaxel cohort, 6 in nab-paclitaxel cohort) had been treated; median (range) follow-up duration was 9.9 mo (0.418.2 mo). 2 DLT occurred in paclitaxel cohort (2 Grade 3 febrile neutropenia) during the DLT evaluation period. At the time of data cutoff, ≥Gr 3 treatment-related AEs occurred in 78.6%, no treatment-related death occurred. ORR was 50.0% in both paclitaxel and nab-paclitaxel regardless of pembro dose or PDL1 status. Conclusions: Pembro plus standard chemotherapy regimens is feasible and yields substantial clinical efficacy regardless of PDL1 status in treatment-naive advanced NSCLC. Detailed survival and safety will be presented.