P024 KEYNOTE-937 trial in progress: adjuvant pembrolizumab for hepatocellular carcinoma and complete radiologic response after surgical resection or local ablation

<h3>Introduction</h3> Hepatocellular carcinoma (HCC) is a leading cause of cancer-related deaths worldwide. Surgical resection and local ablation are potentially curative options for patients with HCC; however, tumor recurrence is not uncommon. The lack of a standard-of-care adjuvant therapy for HCC highlights an urgent therapeutic need to prevent disease recurrence and improve overall survival. Pembrolizumab, a PD-1 inhibitor, has shown evidence of a favorable benefit-to-risk profile in the adjuvant setting for many tumor types but has not been investigated in HCC. The KEYNOTE-937 study (NCT03867084) will evaluate the safety and efficacy of pembrolizumab versus placebo as adjuvant therapy in patients with HCC who had a complete radiologic response after surgical resection or local ablation. <h3>Methods</h3> KEYNOTE-937 is a randomized, double-blind, phase 3 study. Adults with confirmed HCC, complete radiologic response after surgical resection or local ablation, Eastern Cooperative Oncology Group performance status of 0 or 1, and Child-Pugh liver class A are eligible. Patients with past or ongoing hepatitis C or controlled hepatitis B virus infection may be enrolled if they meet prespecified criteria. Patients will be randomly assigned 1:1 to receive pembrolizumab 200 mg intravenously or placebo intravenously every 3 weeks for up to 17 cycles or until disease recurrence, unacceptable toxicity, or withdrawal and will be stratified by geographic region, prior local therapy (resection vs ablation), recurrence risk, and alpha-fetoprotein level at diagnosis. Coprimary end points are recurrence-free survival and overall survival; secondary end points are safety and tolerability (graded per National Cancer Institute Common Terminology Criteria for Adverse Events, version 4.0) and health-related quality of life; exploratory end points include distant metastasis-free survival, time to recurrence, and genomic, metabolic, and/or proteomic biomarkers. Tumor imaging will be assessed until recurrence, and adverse events will be recorded up to 30 days after the last dose (90 days for serious adverse events). <h3>Results</h3> Recruitment began in May 2019. The planned sample size is 950 patients. <h3>Discussion</h3> Results of the KEYNOTE-937 study will show the efficacy and safety of pembrolizumab as adjuvant therapy for patients with HCC who had a complete radiologic response after surgical resection or local ablation.