Abstract 1016TiP
Background
Standard of care for intermediate HCC ineligible for curative treatment is locoregional therapy with transarterial chemoembolization (TACE). Lenvatinib, an inhibitor of VEGFRs 1-3, FGFRs 1-4, PDGFR α, RET, and KIT, is a first-line option for advanced HCC. Pembrolizumab is a PD-1 inhibitor; data from a phase Ib trial of lenvatinib plus pembrolizumab showed broad antitumor activity and manageable safety in patients with unresectable intermediate HCC not amenable to TACE. LEAP-012 (NCT04246177) is a randomized, double-blind, phase III trial to investigate lenvatinib plus pembrolizumab vs placebo in combination with TACE in patients with intermediate HCC.
Trial design
Eligible patients are ≥18 y with confirmed HCC localized to the liver without portal vein thrombosis and not amenable to curative treatment. Patients must have ≥1 measurable lesion per RECIST v1.1 and ECOG PS of 0/1. Patients previously treated with locoregional therapy (≤4 weeks) or systemic chemotherapy for HCC are excluded. Approximately 950 patients will be randomly assigned 1:1 to receive oral lenvatinib QD (12 mg ≥60 kg; 8 mg <60 kg) plus IV pembrolizumab 400 mg Q6W plus TACE or oral placebo QD plus IV placebo Q6W plus TACE. Lenvatinib will be administered until progression or unacceptable toxicity; pembrolizumab will be administered for up to 2 years. TACE is limited to 2 treatments per lesion per site-specified modality. Patients will be stratified by study site, α-fetoprotein level, ECOG PS, albumin–bilirubin grade, and tumor burden. Imaging will be performed every 9 weeks. Safety will be assessed throughout the study. Coprimary end points are overall survival and progression-free survival. Secondary end points are objective response rate, disease control rate, duration of response, time to progression, and safety. Exploratory end points include time from randomization to second/subsequent progression, molecular biomarkers, and health-related quality of life. Recruitment for this study began in April 2020.
Clinical trial identification
NCT04246177.
Editorial acknowledgement
Medical writing and/or editorial assistance was provided by Matthew Grzywacz, PhD of the ApotheCom pembrolizumab team (Yardley, PA, USA) and funded by Merck Sharp & Dohme Corp.
Legal entity responsible for the study
Merck Sharp & Dohme Corp.
Funding
Merck Sharp & Dohme Corp.
Disclosure
J.M. Llovet: Advisory/Consultancy, Research grant/Funding (self): Bayer Pharmaceuticals; Advisory/Consultancy, Research grant/Funding (self): Eisai Inc.; Advisory/Consultancy: Merck; Advisory/Consultancy, Research grant/Funding (self): Bristol-Myers Squibb; Advisory/Consultancy: Celsion Corporation; Advisory/Consultancy: Eli Lilly; Advisory/Consultancy: Roche; Advisory/Consultancy: Genentech; Advisory/Consultancy, Research grant/Funding (self): Ipsen; Advisory/Consultancy: Glycotest; Advisory/Consultancy: Nucleix; Advisory/Consultancy: Can-Fite BioPharma; Advisory/Consultancy: Sirtex Medical; Advisory/Consultancy: AstraZeneca; Research grant/Funding (self): Boehringer Ingelheim. A.B. El-Khoueiry: Honoraria (self), Advisory/Consultancy: CytomX Therapeutics; Honoraria (self), Advisory/Consultancy: Bristol-Myers Squibb; Honoraria (self), Advisory/Consultancy: Bayer; Honoraria (self), Advisory/Consultancy: Eisai; Advisory/Consultancy: Roche; Honoraria (self), Advisory/Consultancy: EMD Serono; Honoraria (self), Advisory/Consultancy, Research grant/Funding (self): Merck; Honoraria (self), Advisory/Consultancy: Exelixis; Honoraria (self), Advisory/Consultancy: Pieris Pharmaceuticals; Honoraria (self), Advisory/Consultancy: Agenus; Honoraria (self), Advisory/Consultancy: Gilead Sciences; Honoraria (self), Advisory/Consultancy: AstraZeneca/MedImmune; Honoraria (self): Roche/Genentech; Research grant/Funding (self): AstraZeneca; Research grant/Funding (self): Astex Pharmaceuticals. A. Vogel: Honoraria (self), Advisory/Consultancy, Research grant/Funding (self): Novartis; Honoraria (self), Advisory/Consultancy: Lilly; Honoraria (self), Advisory/Consultancy, Travel, accommodations, expenses: Roche; Honoraria (self), Advisory/Consultancy: Amgen; Advisory/Consultancy, Travel, accommodations, expenses: Bayer; Advisory/Consultancy: Baxalta; Advisory/Consultancy: AstraZeneca; Advisory/Consultancy: Eisai; Advisory/Consultancy: BTG; Honoraria (self), Advisory/Consultancy, Travel, accommodations, expenses: Ipsen; Honoraria (self), Advisory/Consultancy: Pierre Fabre; Honoraria (self): Sanofi; Honoraria (self): Delcath Systems; Honoraria (self): Bristol-Myers Squibb; Honoraria (self): MSD; Honoraria (self): Janssen. D.C. Madoff: Shareholder/Stockholder/Stock options: RenovoRX; Advisory/Consultancy, Travel, Accommodations, Expenses: Boston Scientific; Advisory/Consultancy, Travel, Accommodations, Expenses: Guerbet; Advisory/Consultancy, Travel, Accommodations, Expenses: Quantum Surgical. R.S. Finn: Advisory/Consultancy, Research grant/Funding (institution): Pfizer; Advisory/Consultancy, Research grant/Funding (institution): Bayer; Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution): Novartis; Advisory/Consultancy, Research grant/Funding (institution): Bristol-Myers Squibb; Advisory/Consultancy, Research grant/Funding (institution): Merck; Advisory/Consultancy, Research grant/Funding (institution): Eisai; Advisory/Consultancy, Research grant/Funding (institution): Lilly; Advisory/Consultancy, Research grant/Funding (institution): Genentech/Roche; Advisory/Consultancy: AstraZeneca; Advisory/Consultancy: Exelixis; Advisory/Consultancy: C Stone Pharma. S. Ogasawara: Honoraria (self), Advisory/Consultancy, Research grant/Funding (self): Bayer; Honoraria (self), Advisory/Consultancy, Research grant/Funding (self): Eisai; Advisory/Consultancy: Merck; Advisory/Consultancy: Chugai Pharma; Advisory/Consultancy: AstraZeneca; Honoraria (self), Advisory/Consultancy: Lilly. Z. Ren: Honoraria (self), Advisory/Consultancy: AstraZeneca; Honoraria (self), Advisory/Consultancy: Merck. K. Mody: Full/Part-time employment: Eisai. J. Jing Li: Shareholder/Stockholder/Stock options, Full/Part-time employment: Merck & Co., Inc.; Spouse/Financial dependant, Employment & stocks (immediate family member): Bristol-Myers Squibb. A.B. Siegel: Shareholder/Stockholder/Stock options, Full/Part-time employment: Merck & Co., Inc.. L. Dubrovsky: Shareholder/Stockholder/Stock options, Full/Part-time employment: Merck & Co., Inc.. M. Kudo: Honoraria (self), Advisory/Consultancy: MSD; Honoraria (self), Advisory/Consultancy: Eisai; Advisory/Consultancy: Ono Pharmaceutical; Advisory/Consultancy: Bristol-Myers Squibb; Honoraria (self): Bayer; Research grant/Funding (institution): Otsuka; Research grant/Funding (institution): Taiho Pharmaceutical; Research grant/Funding (institution): AbbVie; Research grant/Funding (institution): Takeda; Research grant/Funding (institution): Gilead Sciences; Research grant/Funding (institution): EA Pharma.