Phase I Study of Fianlimab, a Human Lymphocyte Activation Gene-3 (LAG-3) Monoclonal Antibody, in Combination With Cemiplimab in Advanced Melanoma

作者：Omid Hamid, Karl D. Lewis, Amy Weise, Meredith McKean, Kyriakos P. Papadopoulos, John Crown, Tae Min Kim, Dae Ho Lee, Sajeve Thomas, Janice M. Mehnert, John M. Kaczmar, Nehal J. Lakhani, Kevin B. Kim, Mark R. Middleton, Guilherme Rabinowits, Alexander I. Spira, Melinda Yushak, Inderjit Mehmi, Fang Fang, Shuquan Chen, Jayakumar Mani, Vladimir Janković, Fang Wang, Nathalie Fiaschi, Laura K. Brennan, Anne Paccaly, Sheila Masinde, Mark Salvati, Matthew G. Fury, Glenn S. Kroog, Israel Lowy, Giuseppe Gullo · 发表于：Journal of Clinical Oncology · 年份：2024 · DOI：10.1200/jco.23.02172 · 被引用次数：41 · 研究领域：Cancer Immunotherapy and Biomarkers、CAR-T cell therapy research、Immunotherapy and Immune Responses

PURPOSE: Coblockade of lymphocyte activation gene-3 (LAG-3) and PD-1 receptors could provide significant clinical benefit for patients with advanced melanoma. Fianlimab and cemiplimab are high-affinity, human, hinge-stabilized IgG4 monoclonal antibodies, targeting LAG-3 and PD-1, respectively. We report results from a first-in-human phase-I study of fianlimab and cemiplimab safety and efficacy in various malignancies including advanced melanoma. METHODS: Patients with advanced melanoma were eligible for enrollment into four cohorts: three for patients without and one for patients with previous anti-PD-1 therapy in the advanced disease setting. Patients were treated with fianlimab 1,600 mg and cemiplimab 350 mg intravenously once every 3 weeks for up to 51 weeks, with an optional additional 51 weeks if clinically indicated. The primary end point was objective response rate (ORR) per RECIST 1.1 criteria. RESULTS: ORRs were 63% for patients with anti-PD-1-naïve melanoma (cohort-6; n = 40; median follow-up 20.8 months), 63% for patients with systemic treatment-naïve melanoma (cohort-15; n = 40; 11.5 months), and 56% for patients with previous neo/adjuvant treatment melanoma (cohort-16; n = 18, 9.7 months). At a median follow-up of 12.6 months for the combined cohorts (6 + 15 + 16), the ORR was 61.2% and the median progression-free survival (mPFS) 13.3 months (95% CI, 7.5 to not estimated [NE]). In patients (n = 13) with previous anti-PD-1 adjuvant therapy, ORR was 61.5% and mPFS ...