Abstract 973TiP
Background
Pembrolizumab, a PD-1 inhibitor, is approved as first-line (1L) monotherapy for pts with R/M HNSCC whose tumors have PD-L1 combined positive score (CPS) ≥1. Lenvatinib, a multikinase inhibitor, plus pembrolizumab was well tolerated and showed antitumor activity in HNSCC (objective response rate [ORR], 46%) in a phase Ib/II trial (NCT02501096). 1L pembrolizumab + lenvatinib will be evaluated in this randomized, double-blind, placebo-controlled, phase III study of pts with R/M HNSCC and PD-L1 CPS ≥1 (LEAP-010).
Trial design
Eligible pts are aged ≥18 years with histologically confirmed R/M HNSCC (oral cavity, oropharynx, hypopharynx, or larynx) incurable by local therapies, tumor PD-L1 CPS ≥1 (central laboratory), with oropharyngeal human papillomavirus (HPV) status, and ECOG performance status (PS) 0 or 1. Approximately 500 pts will be randomized 1:1 to lenvatinib (20 mg orally once daily) + pembrolizumab (200 mg intravenously every 3 weeks) or placebo + pembrolizumab. Randomization will be stratified by PD-L1 tumor proportion score (<50% vs ≥50%), oropharyngeal HPV status (positive vs negative), and ECOG PS (0 vs 1). Treatment will continue ≤2 years for pembrolizumab, until disease progression or unacceptable toxicity. Treatment with lenvatinib or placebo may continue after completion of pembrolizumab treatment. Radiologic imaging will be performed every 6 weeks during the first year and every 9 weeks thereafter. Reponses will be assessed per RECIST v1.1 by blinded independent central review. Primary endpoints are ORR, progression-free survival, and overall survival. Secondary endpoints are duration of response, safety, and tolerability. Adverse events (AEs; graded per NCI CTCAE v5.0) will be monitored from randomization until 30 days (90 days for serious AEs) after last dose of study drug. Key exploratory endpoints include changes in health-related quality of life, assessed using EORTC QLQ-C30, EORTC QLQ-H&N35, and EQ5D-5L instruments, and biomarkers. Recruitment is currently ongoing.
Clinical trial identification
NCT04199104.
Editorial acknowledgement
Medical writing and editorial assistance was provided by Doyel Mitra, PhD, and Jo Bairzin, PhD, of the ApotheCom pembrolizumab team (Yardley, PA, USA). This assistance was 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
L.L. Siu: Advisory/Consultancy, Research grant/Funding (institution): Merck; Advisory/Consultancy: AstraZeneca/MedImmune; Advisory/Consultancy: MorphoSys; Advisory/Consultancy: Roche; Advisory/Consultancy: Loxo; Advisory/Consultancy: Voronoi; Advisory/Consultancy: Oncorus; Advisory/Consultancy: Symphogen; Advisory/Consultancy, Research grant/Funding (institution): Mirati Therapeutics; Advisory/Consultancy, Research grant/Funding (institution): GlaxoSmithKline; Advisory/Consultancy: Seattle Genetics; Advisory/Consultancy, Leadership role, Leadership role (immediate family member): Treadwell Therapeutics; Advisory/Consultancy: Arvinas; Advisory/Consultancy: Navire; Shareholder/Stockholder/Stock options, Stocks (immediate family member): Agios; Research grant/Funding (institution): Bristol-Myers Squibb; Research grant/Funding (institution): Genentech/Roche; Research grant/Funding (institution): Novartis; Research grant/Funding (institution): Pfizer; Research grant/Funding (institution): MedImmune; Research grant/Funding (institution): AstraZeneca; Research grant/Funding (institution): Boehringer Ingelheim; Research grant/Funding (institution): Bayer; Research grant/Funding (institution): Amgen; Research grant/Funding (institution): Astellas Pharma; Research grant/Funding (institution): Shattuck Labs; Research grant/Funding (institution): Symphogen; Research grant/Funding (institution): AVID Radiopharmaceuticals; Research grant/Funding (institution): Intensity Therapeutics; Research grant/Funding (institution): Karyopharm Therapeutics. B. Burtness: Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Merck; Advisory/Consultancy, Travel/Accommodation/Expenses: Debiopharm Group; Honoraria (self), Advisory/Consultancy: AstraZeneca; Advisory/Consultancy, Research grant/Funding (institution): Bristol-Myers Squibb; Advisory/Consultancy: Alligator Bioscience; Advisory/Consultancy, Research grant/Funding (institution): Aduro Biotech; Advisory/Consultancy: GlaxoSmithKline; Advisory/Consultancy: Celgene; Advisory/Consultancy: CUE Biopharma; Advisory/Consultancy: Maverick Therapeutics; Advisory/Consultancy: Rakuten Medical; Advisory/Consultancy: Nanobiotix; Advisory/Consultancy: Macrogenics; Advisory/Consultancy: ALX Oncology; Travel/Accommodation/Expenses: Boehringer Ingelheim; Research grant/Funding (institution): Formation Biologics; Research grant/Funding (institution): Exelixis. E.E. Cohen: Advisory/Consultancy: ALX Oncology; Advisory/Consultancy: Ascendis Pharma; Advisory/Consultancy: Bayer; Advisory/Consultancy: BioLineRx; Advisory/Consultancy: Bristol-Myers Squibb; Advisory/Consultancy: Debiopharm Group; Advisory/Consultancy: Dynavax Technologies; Advisory/Consultancy: MSD; Advisory/Consultancy: Merck; Advisory/Consultancy: Regeneron; Advisory/Consultancy: Sanofi. K.J. Harrington: Honoraria (institution), Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution): Merck Sharp & Dohme; Honoraria (self), Honoraria (institution), Advisory/Consultancy, Speaker Bureau/Expert testimony: Merck Serono; Honoraria (institution), Advisory/Consultancy: AstraZeneca/MedImmune; Honoraria (self), Honoraria (institution), Advisory/Consultancy, Research grant/Funding (self), Research grant/Funding (institution): Boehringer Ingelheim; Honoraria (self), Honoraria (institution), Advisory/Consultancy, Speaker Bureau/Expert testimony: Bristol-Myers Squibb; Honoraria (institution), Advisory/Consultancy: Pfizer; Honoraria (self), Honoraria (institution), Advisory/Consultancy, Research grant/Funding (institution): Replimune; Honoraria (institution): Amgen; Honoraria (self), Honoraria (institution), Advisory/Consultancy: Oncolys BioPharma; Honoraria (institution): Mersana; Honoraria (self), Advisory/Consultancy, Research grant/Funding (self), Research grant/Funding (institution): AstraZeneca; Honoraria (self), Advisory/Consultancy, Research grant/Funding (self), Research grant/Funding (institution): MSD Brazil; Honoraria (self), Advisory/Consultancy: Pfizer Pharmaceuticals Israel. L.F. Licitra: Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: AstraZeneca; Advisory/Consultancy, Travel/Accommodation/Expenses: Bayer; Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: BMS; Advisory/Consultancy, Research grant/Funding (institution): Boehringer Ingelheim; Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Eisai; Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Merck Serono; Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: MSD; Advisory/Consultancy, Research grant/Funding (institution): Novartis; Advisory/Consultancy, Research grant/Funding (institution): Roche; Advisory/Consultancy, Research grant/Funding (institution): Debiopharm International SA; Advisory/Consultancy: Sobi; Advisory/Consultancy: Ipsen; Advisory/Consultancy: Incyte Biosciences Italy srl; Advisory/Consultancy: GSK; Advisory/Consultancy: Doxa Pharma; Advisory/Consultancy: Nanobiotix; Research grant/Funding (institution): Celgene International; Research grant/Funding (institution): Exelixis; Research grant/Funding (institution): Hoffmann-La Roche Ltd; Research grant/Funding (institution): IRX Therapeutics; Research grant/Funding (institution): Medspace; Research grant/Funding (institution): Pfizer. D. Rischin: Research grant/Funding (self), Travel/Accommodation/Expenses: Merck; Research grant/Funding (self): Regeneron; Research grant/Funding (self): Genentech/Roche; Research grant/Funding (self): Bristol-Myers Squibb; Research grant/Funding (self): GlaxoSmithKline. Y. Zhu, C. Pinheiro: Full/Part-time employment: Merck & Co., Inc. C.E. Okpara: Full/Part-time employment: Eisai Europe Ltd. R.F. Swaby: Shareholder/Stockholder/Stock options, Full/Part-time employment: Merck & Co., Inc. J-P. Machiels: Advisory/Consultancy: Boehringer Ingelheim; Advisory/Consultancy, Travel/Accommodation/Expenses: Pfizer; Advisory/Consultancy: Merck Sharp & Dohme; Advisory/Consultancy: Debiopharm Group; Advisory/Consultancy: Nanobiotix; Advisory/Consultancy: Innate Pharma; Advisory/Consultancy: Roche; Advisory/Consultancy: AstraZeneca; Advisory/Consultancy, Research grant/Funding (self): Bayer; Advisory/Consultancy: Merck Serono; Advisory/Consultancy, Travel/Accommodation/Expenses: Bristol-Myers Squibb; Advisory/Consultancy, Research grant/Funding (self): Novartis; Advisory/Consultancy: Incyte; Advisory/Consultancy, Research grant/Funding (self): Janssen; Advisory/Consultancy: CUE Biopharma; Advisory/Consultancy: ALX Oncology; Travel/Accommodation/Expenses: Amgen; Travel/Accommodation/Expenses: MSD; Research grant/Funding (self): Sanofi. M. Tahara: Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Ono Pharmaceutical; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): MSD; Advisory/Consultancy, Research grant/Funding (institution): Pfizer; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Bristol-Myers Squibb; Advisory/Consultancy: Celgene; Advisory/Consultancy: Amgen; Advisory/Consultancy: Rakuten Medical; Advisory/Consultancy, Research grant/Funding (institution): Bayer; Honoraria (self): Merck Serono; Honoraria (self): Eisai; Honoraria (self), Research grant/Funding (institution): AstraZeneca; Research grant/Funding (institution): Novartis; Research grant/Funding (institution): Loxo; Research grant/Funding (institution): Rakuten Medical.