Abstract
PurposeTransarterial chemoembolization (TACE) is the standard of care for patients with intermediate-stage hepatocellular carcinoma (HCC). Lenvatinib, a multikinase inhibitor, and pembrolizumab, a PD-1 inhibitor, have shown efficacy and tolerability in patients with HCC, and adding this combination to TACE may enhance clinical benefit.ProtocolLEAP-012 is a prospective, double-blind randomized phase 3 study. Adults with confirmed HCC localized to the liver without portal vein thrombosis and not amenable to curative treatment, ≥ 1 measurable tumor per Response Evaluation Criteria in Solid Tumors 1.1 (RECIST 1.1), Eastern Cooperative Oncology Group performance status 0 or 1, Child–Pugh class A and no previous systemic treatment for HCC are eligible. Patients will be randomly assigned to lenvatinib once daily plus pembrolizumab every 6 weeks plus TACE or placebos plus TACE. Dual primary endpoints are overall survival and progression-free survival per RECIST 1.1 by blinded independent central review (BICR). Secondary endpoints are progression-free survival, objective response rate, disease control rate, duration of response and time to progression per modified RECIST by BICR; objective response rate, disease control rate, duration of response and time to progression per RECIST 1.1 by BICR; and safety.StatisticsThe planned sample size, 950 patients, was calculated to permit accumulation of sufficient overall survival events in 5 years to achieve 90% power for the overall survival primary endpoint.DiscussionLEAP-012 will evaluate the clinical benefit of adding lenvatinib plus pembrolizumab to TACE in patients with intermediate-stage HCC not amenable to curative treatment.ClinicalTrials.gov NCT04246177.
Highlights
Liver cancer is a leading cause of cancer-related mortality globally [1, 2]
There is an urgent need for novel therapies to improve outcome in this heterogeneous patient population
Stratification by study site was selected to minimize the effect of variations in Transarterial chemoembolization (TACE) technique, instrumentation/imaging and other potential procedure-related heterogeneity across study sites
Summary
Liver cancer is a leading cause of cancer-related mortality globally [1, 2]. The most common primary liver cancer is hepatocellular carcinoma (HCC), accounting for up to 90% of all cases [1, 3]. Survival benefit of TACE alone has been demonstrated in patients with intermediate HCC, in the 50% of whom achieve objective response [10,11,12], there is evidence that patients with high tumor burden or who do not respond to TACE do not derive clinical benefit from this procedure [13, 14]. It is formally contraindicated in certain patients, e.g., patients with macrovascular invasion or liver failure [4, 6, 8]. We describe the rationale and design for the prospective, double-blind, randomized phase 3 LEAP-012 study (NCT04246177), which is being conducted to investigate the efficacy and safety of lenvatinib plus pembrolizumab in combination with TACE compared with TACE alone in patients with intermediate-stage HCC not amenable to curative treatment
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