Phase III LEAP-012 Study Shows Promising Results for Intermediate-Stage HCC Treatment

The LEAP-012 study, a randomized, multicenter, double-blind, phase 3 trial, evaluated the efficacy and safety of lenvatinib (len) plus pembrolizumab (pembro) combined with transarterial chemoembolization (TACE) versus placebo plus TACE in patients with intermediate-stage hepatocellular carcinoma (HCC). The trial involved 480 patients, randomized to receive either len + pembro + TACE or placebo + TACE. The primary endpoints were progression-free survival (PFS) and overall survival (OS).

At the first interim analysis, the median PFS was significantly improved in the len + pembro group (14.6 months) compared to the placebo group (10.0 months), with a hazard ratio (HR) of 0.66 (95% CI, 0.51-0.84; P = 0.0002). However, the OS data were immature, and the significance threshold was not met (HR, 0.80; 95% CI, 0.57-1.11; P = 0.0867).

Grade 3-5 treatment-related adverse events (TRAEs) were more common in the len + pembro group (71.3%) than in the placebo group (31.5%), leading to discontinuation of both study drugs in 8.4% vs 1.2% of patients, respectively. The adverse event profile was consistent with the known safety profiles of lenvatinib, pembrolizumab, and TACE.

The study concluded that the combination of lenvatinib, pembrolizumab, and TACE met its primary endpoint, showing a statistically significant and clinically meaningful improvement in PFS and an early trend toward improvement in OS compared to placebo plus TACE in patients with intermediate-stage HCC. Further analyses are planned to reassess OS outcomes.