Abstract CT284: Phase 3 KEYNOTE-937: Adjuvant pembrolizumab versus placebo in patients with hepatocellular carcinoma and complete radiologic response after surgical resection or local ablation

Background: For patients with hepatocellular carcinoma (HCC) who are undergoing potentially curative surgical resection or local ablation, 5-year recurrence rates are up to 50%-80%; there is no standard of care for adjuvant treatment. The programmed death 1 inhibitor pembrolizumab is approved for the treatment of patients with HCC previously treated with sorafenib. There is 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 3 trial to examine the safety and efficacy of adjuvant pembrolizumab versus placebo in patients with complete radiologic response after surgical resection or local ablation of HCC. Methods: Eligible patients are aged ≥18 years and have confirmed HCC, complete radiologic response after complete resection or local ablation, Eastern Cooperative Oncology Group performance status of 0, and class A Child-Pugh score. Patients with past or ongoing HCV or controlled HBV are eligible if they meet certain criteria. Patients (N~950) will be randomly assigned 1:1 to receive pembrolizumab 200 mg or placebo every 3 weeks and stratified by geographic region, prior local therapy (resection vs ablation), recurrence risk, and alpha-fetoprotein level at diagnosis. Treatment will continue for up to 17 cycles (~1 year) or until documented disease recurrence, unacceptable toxicity, or investigator/patient decision to withdraw. Dual primary end points are recurrence free survival (RFS) and overall survival. Secondary end points are safety, tolerability, and quality of life. Exploratory end points include distant metastases-free survival (DMFS); time to recurrence (TTR); and genomic, metabolic, and/or proteomic biomarkers. RFS, DMFS, and TTR will be assessed radiographically by the investigator and/or by subsequent biopsy and confirmed by blinded independent central review. Adverse events (AEs), 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). Citation Format: Andrew Zhu, Masatoshi Kudo, Arndt Vogel, Thomas Yau, Jian Zhou, Eunhee Kim, Usha Malhotra, Abby B. Siegel, Ann-Lii Cheng. Phase 3 KEYNOTE-937: Adjuvant pembrolizumab versus placebo in patients with hepatocellular carcinoma and complete radiologic response after surgical resection or local ablation [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr CT284.