Multinational phase 3 trial of first-line pembrolizumab with or without lenvatinib for R/M HNSCC

The multinational phase 3 LEAP-010 study evaluated addition of the multikinase inhibitor lenvatinib to first-line pembrolizumab for recurrent or metastatic squamous cell carcinoma (R/M HNSCC) with a PD-LI combined positive score ≥ 1. Adult participants deemed incurable by local therapy were randomized 1:1 to lenvatinib plus pembrolizumab once every 3 weeks for ≤ 35 cycles (n=256) or placebo plus pembrolizumab once every 3 weeks for ≤ 35 cycles (n=255). Primary endpoints were objective response rate (ORR), progression-free survival (PFS), and overall survival (OS). Median time from randomization to data cutoff was 11.5 months for the first interim analysis (IA) and 21.3 months for the second IA. At IA1, the median PFS was 6.2 months in the lenvatinib plus pembrolizumab group versus 2.8 months in the placebo plus pembrolizumab group (HR 0.63; p=0.0001) and the ORR was 46.1% versus 25.4%, respectively (p=0.00002). At IA2, median OS was 15.0 months with lenvatinib plus pembrolizumab compared with 17.9 months with placebo plus pembrolizumab (HR 1.15; p=0.882). At IA2, the incidence of grade 3-4 all cause adverse events was 66.9% with lenvatinib plus pembrolizumab compared with 38.8% with placebo plus pembrolizumab. The authors conclude that addition of lenvatinib to first-line pembrolizumab for R/M HNSCC was associated with improved ORR and PFS, but not OS.