Abstract 1235TiP
Background
Pembrolizumab has demonstrated robust and durable antitumor activity in patients with advanced non‒small-cell lung cancer (NSCLC), both as a monotherapy in the first- and second-line settings (in patients with PD-L1 tumor proportion score [TPS] ≥1%) and as first-line therapy when combined with platinum-based chemotherapy (irrespective of PD-L1 expression). KEYNOTE-671 (ClinicalTrials.gov, NCT03425643) is an international randomized, double-blind, placebo-controlled phase 3 study that evaluates standard neoadjuvant chemotherapy with perioperative pembrolizumab or placebo in early-stage NSCLC.
Trial design
Eligible patients are ≥18 years with previously untreated, resectable locally advanced NSCLC, ECOG PS 0/1, and with a tumor sample for evaluation of PD-L1 expression. Patients are randomized 1:1 to neoadjuvant chemotherapy (cisplatin 75 mg/m2 with gemcitabine 1000 mg/m2 [days 1 and 8; squamous histology] or pemetrexed 500 mg/m2 [nonsquamous histology]) plus either pembrolizumab 200 mg or placebo Q3W for 4 cycles, followed by surgery, then adjuvant pembrolizumab 200 mg or placebo Q3W for 13 cycles. Randomization is stratified by disease stage, PD-L1 TPS <50% vs ≥50%, squamous vs nonsquamous, and East Asia vs non-East Asia. Radiographic response is assessed by RECIST version 1.1 per blinded independent central review 3 weeks after cycles 2 and 4, and every 16 weeks from date of randomization in the adjuvant phase. Disease recurrence/progression is confirmed by biopsy. Adverse events are graded per NCI-CTCAE version 4.0 or later. Primary endpoints are event-free survival (time from randomization to first of disease/local progression, unresectable tumor, local/distant recurrence, or death) and overall survival (time from randomization to all-cause death). Secondary endpoints are major pathologic response (≤10% viable tumor cells in resected primary tumor/lymph nodes), pathologic complete response (no residual invasive cancer on H&E stained slides of resected lung specimen/lymph nodes post–neoadjuvant therapy), safety, and patient-reported outcomes. An estimated 786 patients will be enrolled. Enrollment began March 9, 2018.
Clinical trial identification
NCT03425643.
Editorial acknowledgement
Writing support was provided by Christabel Wilson, MSc, of ICON plc (North Wales, PA, USA), funded by Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.
Legal entity responsible for the study
Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.
Funding
Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.
Disclosure
M. Tsuboi: Advisory/Consultancy: AstraZeneca and MSD; Honoraria (self), received honorarium from promotional activities: AstraZeneca KK, Bristol-Myers Squibb Japan, Ono Pharmaceutical Co., Ltd., Eli Lilly Japan, MSD Japan, Taiho Pharma, Johnson & Johnson Japan, Medtronic Japan, Teijin Pharma, Chugai Pharmaceutical CO.,LTD; Research grant/Funding (institution): Boehringer Ingelheim Japan, AstraZeneca KK, MSD Japan, Bristol-Myers Squibb Japan, Ono Pharmaceutical Co., Ltd. T. Kato: Advisory/Consultancy: AstraZeneca, Chugai, Eli Lilly, MSD, Pfizer; Honoraria (self): AbbVie, AstraZeneca, Boehringer Ingelheim, Chugai, Eli Lilly, F. Hoffman-La Roche, Merck Serono, MSD, Nitto Denko, Novartis, Ono, Pfizer, Sumitomo Dainippon, Taiho, Takeda; Research grant/Funding (institution): AbbVie, AstraZeneca, Chugai, Eli Lilly, Kyorin, Merck Serono, MSD, Novartis, Ono, Pfizer, Regeneron, and Taiho. B. Zurawski: Honoraria (self): AstraZeneca, Boehringer Ingelheim, F. Hoffman-La Roche, Merck Serono, MSD, BMS, Novartis, Pfizer, Astellas; Research grant/Funding (institution): BMS, AstraZeneca, Boehringer Ingelheim, F. Hoffman-La Roche, Merck Serono, MSD, Novartis, Pfizer. I. Demedts: Advisory/Consultancy: MSD, BMS, AstraZeneca, Roche, Boehringer Ingelheim; Research grant/Funding (institution): MSD, BMS, AstraZeneca, Roche, Boehringer Ingelheim. M.C. Garassino: Research grant/Funding (institution): Merck, BMS, AstraZeneca, Roche, Celgene, and MedImmune; Honoraria (self), received personal fees: Merck, BMS, AstraZeneca, Roche, Celgene, MedImmune, Incyte, Ignyta. J. Yang: Full/Part-time employment: Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA. K. Makarious: Full/Part-time employment: Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA. S.M. Keller: Full/Part-time employment: Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA. H.A. Wakelee: Advisory/Consultancy, advisory board participation (compensated): Janssen (April 2019), Mirati (ongoing), Daiichi Sankyo (Sept 2019), Helsinn (ongoing); Advisory/Consultancy, advisory board (NOT compensated): Merck, Genentech/Roche, Cellworks; Research grant/Funding (institution): ACEA Biosciences, Arrys Therapeutics, AstraZeneca/MedImmune, BMS, Celgene, Clovis Oncology, Exelixis, Genentech/Roche, Gilead, Lilly, Merck, Novartis, Pfizer, Pharmacyclics, Xcovery. All other authors have declared no conflicts of interest.