Randomized, double-blind, phase III LEAP-003 study of first-line lenvatinib plus pembrolizumab versus placebo plus pembrolizumab for unresectable or metastatic melanoma

作者：Ana Arance, Miguel‐Ángel Berciano‐Guerrero, Jun Guo, M.S. Carlino, Paolo A. Ascierto, Mauricio Burotto, Laurent Mortier, P. Queirolo, Vanna Chiarion‐Sileni, Jacob Schachter, Xiang Zhang, J. Martin-Liberal, M. Del Vecchio, Chinyere E. Okpara, Corina E. Dutcus, Jie Zhang, Scott J. Diede, Tobias Neff, Georgina V. Long · 发表于：Annals of Oncology · 年份：2025 · DOI：10.1016/j.annonc.2025.08.008 · 被引用次数：8 · 研究领域：Cancer Immunotherapy and Biomarkers、Melanoma and MAPK Pathways、CAR-T cell therapy research

BACKGROUND: Lenvatinib plus pembrolizumab demonstrated antitumor activity in advanced melanoma after prior anti-programmed cell death protein or ligand 1 [PD-(L)1] therapy in LEAP-004. Here, we report results from LEAP-003 (NCT03820986) which evaluated first-line lenvatinib plus pembrolizumab versus placebo plus pembrolizumab in unresectable advanced melanoma. PARTICIPANTS AND METHODS: Participants with unresectable stage III or IV melanoma, previously untreated with PD-(L)1 inhibitors were randomly assigned 1 : 1 to pembrolizumab 200 mg intravenously every 3 weeks plus either lenvatinib 20 mg or placebo orally once daily. Dual primary endpoints were progression-free survival (PFS) per RECIST v1.1 by blinded independent central review and overall survival (OS). PFS was formally tested at the first interim analysis; OS at the final analysis. An external data monitoring committee regularly reviewed safety and efficacy. Three interim analyses and a final analysis were planned. RESULTS: Overall, 674 participants were assigned to lenvatinib plus pembrolizumab (n = 334) or placebo plus pembrolizumab (n = 340). Median PFS at first interim analysis was 8.4 months for lenvatinib plus pembrolizumab versus 4.0 months for placebo plus pembrolizumab [hazard ratio (HR) 0.72, 95% confidence interval (CI) 0.59-0.88, P = 0.0008]. This benefit was not maintained at final analysis (HR 0.83, 95% CI 0.69-1.00). Median OS at final analysis was 25.8 months for lenvatinib plus pembrolizumab versus 3...