LBA34 Primary results from the phase III LEAP-002 study: Lenvatinib plus pembrolizumab versus lenvatinib as first-line (1L) therapy for advanced hepatocellular carcinoma (aHCC)

The global, randomized, double-blind, Ph3 LEAP-002 study (NCT03713593) evaluated the efficacy and safety of lenvatinib + pembrolizumab (lenva + pembro) vs lenvatinib (lenva) + placebo as 1L therapy for aHCC. Eligible pts with aHCC were randomized 1:1 to lenva (8 mg/day if BW<60 kg or 12 mg/day if BW≥60 kg) plus pembro (200 mg IV Q3W) or lenva plus placebo. Dual primary endpoints OS and PFS (per RECIST 1.1 by BICR) were assessed using the stratified log-rank test. ORR (per RECIST 1.1 by BICR) was a key secondary endpoint. The protocol specified 2 interim analyses (IAs) and a final analysis (FA) for OS. Prespecified efficacy boundaries were one-sided P = 0.002 for PFS at IA1 (prespecified final PFS analysis) and 0.0185 for OS at FA. 794 pts were randomized (lenva + pembro, 395; lenva, 399). At FA (data cutoff 21 June 2022; median follow-up 32.1 mo), 534 OS events had occurred and 36 pts (9.1%) in the lenva + pembro arm and 24 pts (6.1%) in the lenva arm remained on study treatment. The median OS with lenva + pembro was 21.2 mo vs 19.0 mo with lenva, and the HR was 0.840 (95% CI: 0.708-0.997, P=0.0227, Table). HR for PFS at IA1 (data cutoff 5 April 2021) was 0.867 (95% CI: 0.734-1.024, P=0.0466, Table). ORR at FA was 26.1% for lenva + pembro vs 17.5% for lenva. Grade 3-5 treatment-related adverse events (TRAEs) were 62.5% in the lenva + pembro arm and 57.5% in the lenva arm (grade 5 TRAEs, 1.0% vs 0.8%). Post-study systemic anti-cancer treatments were used in 44.1% vs 52.1% of pts, in each arm, respectively.Table: LBA34Lenva + Pembro (N=395)Lenva (N=399)OS at FAMedian (95% CI), mo21.2 (19.0-23.6)19.0 (17.2-21.7) HR (95% CI), P0.840 (0.708-0.997), P=0.0227PFS at IA1Median (95% CI), mo8.2 (6.4-8.4)8.0 (6.3-8.2) HR (95% CI), P0.867 (0.734-1.024), P=0.0466PFS at FAMedian (95% CI), mo8.2 (6.3-8.3)8.1 (6.3-8.3) HR (95% CI)0.834 (0.712-0.978)ORR at FA% (95% CI)26.1 (21.8-30.7)17.5 (13.9-21.6) Open table in a new tab LEAP-002 primary endpoints of OS (at FA) and PFS (at IA1) did not meet pre-specified statistical significance. The combination of lenva + pembro achieved the longest median OS ever reported in 1L HCC Ph3 studies (21.2 mo) with no new safety signals observed. The median OS of 19.0 mo with lenva monotherapy supports its role as a standard of care in 1L aHCC.