Abstract 1418TiP
Background
In KEYNOTE-407, 1L pembro + carboplatin-(nab)paclitaxel (chemo) significantly improved OS in metastatic sqNSCLC. The poly(ADP-ribose) polymerase inhibitor olaparib improved outcomes as maintenance therapy vs placebo in platinum-sensitive, newly diagnosed BRCA1/BRCA2–mutated (BRCAm) ovarian cancer and relapsed/recurrent BRCAm/BRCA wild-type ovarian cancer, suggesting efficacy in tumors with homologous recombination repair deficiency (HRD) regardless of BRCAm. High HRD scores in NSCLC suggest potential benefit with olaparib maintenance in pts with NSCLC. KEYLYNK-008 (NCT03976362) evaluates pembro ± maintenance olaparib after pembro + chemo induction as 1L treatment in pts with metastatic sqNSCLC.
Trial design
This randomized, double-blind, placebo-controlled phase 3 study enrolls pts ≥18 y with treatment-naive histologically/cytologically confirmed metastatic sqNSCLC, with measurable disease (RECIST v1.1), ECOG PS 0/1, and a tumor tissue sample evaluable for PD-L1. All pts (∼735) receive 4 cycles of pembro 200 mg + carboplatin AUC 6 mg/mL/min + paclitaxel 200 mg/m2 or nab-paclitaxel 100 mg/m2 Q3W. Pts with CR, PR, or SD after cycle 4 (∼566 pts) are randomized 1:1 to pembro 200 mg Q3W (up to 31 cycles) + maintenance olaparib 300 mg or placebo BID, stratified by ECOG PS (0 vs 1), PD-L1 TPS (<50% vs ≥50%), and response at randomization (CR/PR vs SD). Tumor imaging (RECIST v1.1; 10 total target lesions max, 5/organ) by central review (BICR) occurs at baseline and Q6W up to wk 48, then Q9W until verified PD, start of new anticancer therapy, or study withdrawal. AEs throughout the study up to 30 days (serious AEs, 90 days) after discontinuing treatment are graded by NCI CTCAE v4.0. Primary endpoints are PFS (RECIST v1.1 by BICR) and OS analyzed by Kaplan-Meier method and stratified log-rank test, with HRs per stratified Cox proportional hazard model with Efron’s tie handling method. Safety and patient reported outcomes are secondary endpoints; ORR and duration of response are exploratory endpoints. Enrollment began on June 28, 2019 at 162 sites in 20 countries.
Clinical trial identification
NCT03976362.
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
J.E. Gray: Honoraria (self), Research grant/Funding (institution): Array, AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Eli Lilly, Genentech, and Merck. T.K. Owonikoko: Advisory/Consultancy: Merck. T. Kato: Full/Part-time employment: Eli Lilly (I); Honoraria (self): Chugai Pharma; Roche; Boehringer Ingelheim; Ono Pharmaceutical; Eli Lilly; AstraZeneca; Taiho Pharmaceutical; Pfizer; Bristol-Myers Squibb Japan; Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA; Novartis; Sumitomo Dainipp; Advisory/Consultancy: AstraZeneca; Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA; Eli Lilly; Chugai Pharma; Nitto Denko; AbbVie; Merck Serono; and Pfizer; Research grant/Funding (institution): Chugai Pharma; Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA; Kyowa Hakko Kirin; Pfizer; Taiho Pharmaceutical; AstraZeneca; Eli Lilly; AbbVie; Astellas Pharma; Ono Pharmaceutical; Merck Serono; Research grant/Funding (self): Kyorin; Regeneron. E. Nadal: Advisory/Consultancy: Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA; Bristol-Myers Squibb; Roche; Takeda; Eli Lilly; AstraZeneca; Boehringer Ingelheim; and Pfizer; Research grant/Funding (institution): Roche and Pfizer. A. Greystoke: Advisory/Consultancy: Pfizer; Boehringer Ingelheim; Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA; Novartis; AstraZeneca; Bristol-Myers Squibb; Takeda; Janssen Oncology; and Eli Lilly; Speaker Bureau/Expert testimony: Boehringer Ingelheim; Roche; Pfizer; Novartis; AstraZeneca; Bristol-Myers Squibb; Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA; AbbVie; Takeda; and Foundation Medicine; Travel/Accommodation/Expenses: Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA; Takeda; and Roche. A.F. Cardona: Honoraria (self), Research grant/Funding (institution): Roche; Boehringer Ingelheim; AstraZeneca; Pfizer; Celldex; Bristol-Myers Squibb; Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA; and AbbVie; Leadership role, Cofounder: Foundation for Clinical and Applied Cancer Research (FICMAC), Bogotá, Colombia. J. Penrod, Z. Wei, H. Lara-Guerra: Full/Part-time employment: Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA. C. Schulz: Advisory/Consultancy: AstraZeneca, BMS, Boehringer Ingelheim, Lilly, MSD, Novartis, Roche, Takeda; Speaker Bureau/Expert testimony: AstraZeneca, BMS, Boehringer Ingelheim, Lilly, MSD, Novartis, Roche, Takeda; Travel/Accommodation/Expenses: AstraZeneca, Boehringer Ingelheim, Roche, Takeda.