Abstract 1017TiP
Background
For patients with HCC undergoing potentially curative surgical resection or local ablation, 5-year recurrence rates are between 50% and 80%; there is currently no standard of care for adjuvant treatment. Pembrolizumab, a programmed death 1 inhibitor, is approved for the treatment of patients with HCC who have previously received sorafenib. There is currently no direct evidence of benefit with pembrolizumab in the HCC adjuvant setting, but a favorable benefit/risk profile is anticipated based on data from other indications. KEYNOTE-937 (NCT03867084) is a randomized, double-blind, phase III trial designed to investigate the safety and efficacy of adjuvant pembrolizumab versus placebo in patients with HCC who have had a complete radiologic response after surgical resection or local ablation.
Trial design
Eligible patients are aged ≥18 yrs with confirmed HCC, complete radiologic response after complete resection or local ablation, ECOG performance status of 0, and class A Child-Pugh score. Patients with past or ongoing HCV or controlled HBV are eligible if they meet prespecified criteria. Approximately 950 patients will be randomly assigned 1:1 to pembrolizumab 200 mg or placebo IV every 3 weeks. Treatment will continue for up to 17 cycles (∼1 year) or until disease recurrence, unacceptable toxicity, or withdrawal. Patients will be stratified by geographic region, prior local therapy (resection vs ablation), recurrence risk, and alpha-fetoprotein level at diagnosis. Co-primary end points are recurrence-free survival and overall survival. Secondary end points are safety and tolerability and health-related quality of life. Exploratory end points include distant metastases-free survival; time to recurrence; and genomic, metabolic, and/or proteomic biomarkers. Tumor imaging will be performed every 12 weeks until recurrence or Week 228 (∼year 4), whichever occurs first. Adverse events, graded per National Cancer Institute Common Terminology Criteria for Adverse Events, version 4.0, will be recorded up to 30 days after last dose (90 days for serious AEs). Recruitment for this study began in May 2019.
Clinical trial identification
NCT03867084.
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
A. Vogel: Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Novartis; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Roche; Honoraria (self): Sanofi; Honoraria (self), Advisory/Consultancy: Amgen; Honoraria (self): Decalth Systems; Honoraria (self), Advisory/Consultancy: Lilly; Honoraria (self): Bristol-Myers Squibb; Honoraria (self): MSD; Honoraria (self), Advisory/Consultancy: Pierre Fabre; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Ipsen; Honoraria (self): Janssen; Advisory/Consultancy, Travel/Accommodation/Expenses: Bayer; Advisory/Consultancy: Baxalta; Advisory/Consultancy: AstraZeneca; Advisory/Consultancy: Eisai; Advisory/Consultancy: BTG. A.X. Zhu: Advisory/Consultancy: Exelixis; Advisory/Consultancy, Research grant/Funding (institution): Merck; Advisory/Consultancy: AstraZeneca; Advisory/Consultancy, Research grant/Funding (institution): Bayer; Advisory/Consultancy, Research grant/Funding (institution): Lilly; Advisory/Consultancy: Eisai; Advisory/Consultancy: Roche/Genentech; Research grant/Funding (institution): Bristol-Myers Squibb; Research grant/Funding (institution): Novartis. A-L. Cheng: Honoraria (self), Advisory/Consultancy: AstraZeneca; Honoraria (self), Advisory/Consultancy: Bristol-Myers Squibb; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony: Eisai; Honoraria (self), Advisory/Consultancy: Merck Serono; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony: Novartis; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony: Ono Pharmaceutical; Honoraria (self), Advisory/Consultancy: Exelixis; Honoraria (self), Advisory/Consultancy: Nucleix; Honoraria (self), Advisory/Consultancy: IPSEN Innovation; Honoraria (self), Advisory/Consultancy: Bayer Healthcare; Honoraria (self), Advisory/Consultancy: Merck Sharp & Dohme; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Roche/Genentech; Honoraria (self), Advisory/Consultancy: BeiGene; Honoraria (self), Advisory/Consultancy: CSR Pharma Group; Honoraria (self), Advisory/Consultancy: F. Hoffmann-La Roche; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: IQVIA; Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: Bayer Yakuhin; Speaker Bureau/Expert testimony: Amgen Taiwan. T. Yau: Honoraria (self): MSD Oncology; Honoraria (self), Advisory/Consultancy: Bristol-Myers Squibb. E. Kim: Full/Part-time employment: Merck & Co., Inc.; Shareholder/Stockholder/Stock options: MSD. U. Malhotra: Full/Part-time employment: Merck & Co., Inc.; Shareholder/Stockholder/Stock options: MSD. A.B. Siegel: Full/Part-time employment: Merck & Co., Inc.; Shareholder/Stockholder/Stock options: MSD. M. Kudo: Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Eisai; Honoraria (self): Bayer; Honoraria (self), Advisory/Consultancy: MSD; Advisory/Consultancy: BMS; Research grant/Funding (institution): EA Pharma; Research grant/Funding (institution): Gilead; Research grant/Funding (institution): Takeda; Research grant/Funding (institution): Otsuka; Research grant/Funding (institution): Taiho; Research grant/Funding (institution): AbbVie; Advisory/Consultancy: Ono. All other authors have declared no conflicts of interest.