Purpose: Limited treatment options are available for patients with intermediate hepatocellular carcinoma (HCC). Lenvatinib, a potent multikinase inhibitor, and pembrolizumab, a programmed death receptor-1 blocking antibody, are approved first- and second-line therapies for advanced HCC, respectively. LEAP-012 (NCT04246177) is investigating lenvatinib plus pembrolizumab in combination with transarterial chemoembolization (TACE) versus placebo plus TACE in patients with intermediate HCC.
Materials and Methods: LEAP-012 is a randomized double-blind phase 3 study. Adults with confirmed HCC localized to the liver without portal vein thrombosis and not amenable to curative treatment, ≥1 measurable lesion per RECIST v1.1, Eastern Cooperative Oncology Group performance status of 0 or 1, and no previous treatment with locoregional therapy or systemic chemotherapy for HCC are eligible. Patients will be randomly assigned to receive lenvatinib 8 (body weight < 60 kg) or 12 mg (body weight ≥60 kg) orally once daily plus pembrolizumab 400 mg intravenously every 6 weeks (Q6W) plus TACE or placebo orally once daily plus placebo intravenously Q6W, plus TACE. Response will be assessed by imaging every 9 weeks, and safety will be assessed throughout the study and up to 90 days after the end of treatment. Coprimary end points are overall survival and progression-free survival (PFS) per RECIST v1.1 by blinded independent central review (BICR). Secondary end points are PFS, objective response rate (ORR), disease control rate (DCR), duration of response (DOR), and time to progression (TTP) per modified RECIST by BICR; ORR, DCR, DOR, and TTP per RECIST v1.1 by BICR; and safety. Exploratory end points are PFS, ORR, DCR, DOR, TTP, and time from randomization to second/subsequent progression per RECIST v1.1 by investigator review, identification of molecular biomarkers, and health-related quality of life.
Results: Recruitment began in April 2020. The planned sample size is 950 patients.
Conclusion: LEAP-012 will elucidate the clinical benefit of adding lenvatinib plus pembrolizumab to the current standard of care TACE for patients with intermediate-stage HCC not amenable to curative treatment.