Abstract 1313P
Background
Pembro + platinum-based chemo is standard 1L therapy for patients (pts) with metastatic NSCLC. In a phase 1b/2 study, pembro + len showed antitumor activity with acceptable safety in multiple tumor types, including metastatic NSCLC treated with ≤2 prior regimens. LEAP-006 (NCT03829319) evaluates 1L pembro + platinum-based chemo ± len in pts with metastatic nonsquamous (nsq) NSCLC. We report the first data from the open-label safety run-in (part 1) of LEAP-006.
Methods
LEAP-006 is a global, randomized, double-blind, placebo (pbo)-controlled, 2-part, phase 3 study enrolling pts aged ≥18 y with metastatic, treatment-naive nsqNSCLC, ECOG PS 0/1, and tumor sample available for PD-L1 expression; and without actionable genetic aberrations. In part 1, pts received len 8 mg/d + pembro 200 mg + pemetrexed (pem) 500 mg/m2 + carboplatin AUC 5 or cisplatin 75 mg/m2 Q3W in cycles 1‒4; then pembro (up to 31 more cycles) with len + pem until PD/toxicity. Dose-limiting toxicities (DLTs; selected prespecified grade ≥3 AEs or prespecified criteria for thrombocytopenia or any grade thromboembolic event) were assessed for 21 d after first dose.
Results
13 pts were enrolled and treated in part 1 (data cutoff, Mar 3, 2020; median study follow-up, 7.5 [range, 5.7–10.3] mo). Pts received a median of 10 (range, 2–12) cycles of therapy. There were 2 DLTs–both grade 3 hyponatremia in pts receiving cisplatin. 10 pts (77%) had grade 3–5 AEs (treatment-related, n = 7 [54%]), 1 (8%) died due to an AE (not treatment-related), and 6 (46%) had immune-mediated AEs. 4 pts (31%) had grade 3 hypertension; none had grade ≥3 proteinuria. There were no infusion reactions. ORR was 69.2% (95% CI, 38.6-90.9; n = 9; all PR); 3 pts (23.1%) had SD. Of 13 pts, 11 were alive and 10 were progression free by BICR. As <3 DLTs occurred in each platinum-containing arm, enrollment into part 2 began, in which pts randomly receive platinum-based chemo + pembro (similar to part 1) with either len or pbo.
Conclusions
Results from part 1 showed acceptable safety and tolerability, and preliminary evidence of antitumor activity with 1L len + pembro + platinum-based chemo in pts with metastatic nsqNSCLC. Enrollment in part 2 is ongoing.
Clinical trial identification
NCT03829319.
Editorial acknowledgement
Medical writing and editorial assistance was provided by Michael S. McNamara, MS, of ICON plc (North Wales, PA, USA). This assistance was co-funded by the study sponsors, Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA, and Eisai Inc., Woodcliff Lake, NJ, USA.
Legal entity responsible for the study
Eisai Inc. and Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.
Funding
Eisai Inc. and Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.
Disclosure
M. Nishio: Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution): Ono Pharmaceutical; Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution): Bristol-Myers Squibb; Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution): Pfizer; Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution): Chugai Pharmaceutical; Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution): Eli Lilly; Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution): Taiho Pharmaceutical; Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution): AstraZeneca; Advisory/Consultancy, Speaker Bureau/Expert testimony: Boehringer Ingelheim; Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution): Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc; Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution): Novartis; Advisory/Consultancy, Speaker Bureau/Expert testimony: Merck Biopharma; Advisory/Consultancy, Speaker Bureau/Expert testimony: Daiichi Sankyo; Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution): Takeda Pharmaceutical Company Limited; Advisory/Consultancy, Speaker Bureau/Expert testimony: Teijin Pharma Limited; Advisory/Consultancy, Speaker Bureau/Expert testimony: AbbVie. N. Peled: Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony: AstraZeneca; Honoraria (self), Speaker Bureau/Expert testimony: Bayer; Honoraria (self), Speaker Bureau/Expert testimony: Boehringer Ingelheim; Honoraria (self), Speaker Bureau/Expert testimony: Bristol-Myers Squibb; Honoraria (self), Speaker Bureau/Expert testimony: Foundation Medicine; Honoraria (self), Speaker Bureau/Expert testimony: Guardant360; Honoraria (self), Speaker Bureau/Expert testimony: Merck; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony: Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony: Novartis; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony: Pfizer; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony: Roche; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony: Takeda; Advisory/Consultancy: Eli Lilly; Advisory/Consultancy, Licensing/Royalties: GeneSort; Advisory/Consultancy, Licensing/Royalties: NovellusDx; Advisory/Consultancy: Takeda. A. Zer: Honoraria (institution), Advisory/Consultancy, Research grant/Funding (institution): Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc.; Honoraria (institution), Advisory/Consultancy, Research grant/Funding (institution): Roche; Honoraria (institution), Advisory/Consultancy, Research grant/Funding (institution): Takeda; Honoraria (institution), Advisory/Consultancy, Research grant/Funding (institution): AZ; Honoraria (institution): BI; Research grant/Funding (institution): BMS. J. Bar: Advisory/Consultancy: Roche; Advisory/Consultancy, Research grant/Funding (institution): AstraZeneca; Advisory/Consultancy, Research grant/Funding (institution): Pfizer; Advisory/Consultancy: Takeda; Advisory/Consultancy: Boehringer Ingelheim; Advisory/Consultancy: Bayer; Advisory/Consultancy, Research grant/Funding (institution): Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc.; Advisory/Consultancy: BMS; Advisory/Consultancy: Novartis; Advisory/Consultancy: AbbVie. R. Herbst: Advisory/Consultancy: AbbVie Pharmaceuticals; Advisory/Consultancy: ARMO Biosciences; Advisory/Consultancy, Research grant/Funding (institution): AstraZeneca; Advisory/Consultancy: Biodesix; Advisory/Consultancy: Bolt Biotherapeutics; Advisory/Consultancy: Bristol-Myers Squibb; Advisory/Consultancy, Research grant/Funding (institution): Eli Lilly and Company; Advisory/Consultancy: EMD Serono; Advisory/Consultancy, Research grant/Funding (institution): Genentech/Roche; Advisory/Consultancy: Genmab; Advisory/Consultancy: Halozyme; Advisory/Consultancy: Heat Biologics; Advisory/Consultancy: IMAB Biopharma; Advisory/Consultancy: Immunocore; Advisory/Consultancy: Loxo Oncology; Advisory/Consultancy, Research grant/Funding (institution): Merck & Co., Inc.; Advisory/Consultancy: Midas Health Analytics; Advisory/Consultancy: Mirati Therapeutics; Advisory/Consultancy: Nektar; Advisory/Consultancy: NextCure; Advisory/Consultancy: Novartis; Advisory/Consultancy: Pfizer; Advisory/Consultancy: Sanofi; Advisory/Consultancy: Seattle Genetics; Advisory/Consultancy: Shire PLC; Advisory/Consultancy: Spectrum Pharmaceuticals; Advisory/Consultancy: Symphogen; Advisory/Consultancy: Takeda; Advisory/Consultancy: Tesaro; Advisory/Consultancy: Tocagen; Advisory/Consultancy: Neon Therapeutics; Advisory/Consultancy: Infinity Pharmaceuticals; Leadership role, non-executive/independent board member : Junshi Pharmaceuticals. D. Rodriguez-Abreu: Advisory/Consultancy, Speaker Bureau/Expert testimony: Roche; Advisory/Consultancy, Speaker Bureau/Expert testimony: AstraZeneca; Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution): Bristol-Myers Squibb; Advisory/Consultancy, Speaker Bureau/Expert testimony: Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc.; Advisory/Consultancy, Speaker Bureau/Expert testimony: Eli Lilly; Advisory/Consultancy, Speaker Bureau/Expert testimony: Pfizer; Advisory/Consultancy, Speaker Bureau/Expert testimony: Novartis. R. Talpur: Full/Part-time employment: Eisai Inc. L. Golden, L. Yin, T. Dang: Full/Part-time employment: Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc. R. Hui: Honoraria (self), Advisory/Consultancy: Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc.; Advisory/Consultancy: AstraZeneca; Advisory/Consultancy: Bristol-Myers Squibb; Advisory/Consultancy: Eli Lilly; Honoraria (self), Advisory/Consultancy: Novartis; Advisory/Consultancy: Roche. All other authors have declared no conflicts of interest.