Behind the LEAP-012 Trial of Lenvatinib, Pembrolizumab, and TACE in HCC

Josep M. Llovet, MD, PhD, director of the Liver Cancer Program and professor of medicine in the Division of Liver Diseases at the Icahn School of Medicine at Mount Sinai Hospital in New York, New York, describes the phase 3 LEAP-012 clinical study (NCT04246177), including its methods, design, and enrollment criteria.

LEAP-012 is a phase 3, double-blinded, active-controlled, multicenter, randomized trial which sought to evaluate lenvatinib (Lenvima) given with pembrolizumab (Keytruda) and transarterial chemoembolization (TACE) vs placebo and TACE in patients with intermediate-stage hepatocellular carcinoma (HCC). A total of 480 patients with intermediate-stage HCC were enrolled and randomly assigned to receive the combination of lenvatinib, pembrolizumab, and TACE (n = 237) or the placebo and TACE regimen (n = 243). Of the patients in each arm, 237 and 241 patients were treated.

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0:09 | At [ESMO 2024], we presented the phase 3 trial, the LEAP-012 trial, comparing lenvatinib plus pembrolizumab plus TACE in patients with intermediate-stage HCC. Intermediate stage represents those patients with liver-only disease without vascular invasion or extroverted spread that account for around 30% of the total population of patients with hepatocellular carcinoma. During the last 20 years, the standard of care has been TACE, and around 15 randomized control trials have been conducted testing combinations of systemic therapies with TACE. All of them unfortunately resulted in negative results.

0:52 | In our study, we randomized 480 patients to receive either the [triplet] treatment of lenvatinib/pembrolizumab/TACE or the dual placebo plus TACE for 2 years. The primary end point was progression-free survival and overall survival, and then secondary end points were objective response rate and duration of response.