Neoadjuvant PD-1 and LAG-3-targeting bispecific antibody and other immune checkpoint inhibitor combinations in resectable melanoma: the randomized phase 1b/2 Morpheus-Melanoma trial

作者：Georgina V. Long, Nitya Nair, Daniel Marbach, Richard A. Scolyer, Sabine Wilson, Denise Cotting, Nicolas Städler, Rodabe N. Amaria, Paolo A. Ascierto, Ahmad A. Tarhini, Caroline Robert, Omid Hamid, Caroline Gaudy‐Marqueste, Célèste Lebbé, Eva Muñoz‐Couselo, Alexander M. Menzies, Cécile Pagès, Giuseppe Curigliano, Mario Mandalà, Nikki Jessop, Uwe Bader, Maurizio Perdicchio, Volker Teichgräber, Merlind Muecke, Christoph Markert, Christian U. Blank · 发表于：Nature Medicine · 年份：2025 · DOI：10.1038/s41591-025-03967-2 · 被引用次数：18 · 研究领域：CAR-T cell therapy research、Cancer Immunotherapy and Biomarkers、Immunotherapy and Immune Responses

Abstract Patients with stage III melanoma are at high risk of relapse. The NADINA trial evaluating neoadjuvant nivolumab plus ipilimumab and the SWOG-1801 trial evaluating neoadjuvant pembrolizumab have demonstrated superior clinical outcomes with neoadjuvant versus adjuvant checkpoint inhibition. Morpheus-Melanoma was a phase 1b/2, randomized umbrella trial evaluating tobemstomig (anti-PD-1/anti-LAG-3 bispecific antibody; n = 40), tobemstomig plus tiragolumab (anti-TIGIT monoclonal antibody; n = 20) and atezolizumab (PD-L1-targeting monoclonal antibody) plus tiragolumab ( n = 20) versus nivolumab (anti-PD-1 monoclonal antibody) plus ipilimumab (anti-CTLA-4 monoclonal antibody; n = 22) in stage III melanoma. The primary endpoint was pathological response by independent pathological review. Additional endpoints included safety and exploratory biomarkers. Here tobemstomig showed a similar pathological response rate (pRR) versus nivolumab plus ipilimumab (80.0% (32/40) versus 77.3% (17/22)); major pathological responses were less frequent with tobemstomig versus nivolumab plus ipilimumab treatment (62.5% (25/40) versus 72.7% (16/22)). Tobemstomig plus tiragolumab and atezolizumab plus tiragolumab showed a lower pRR versus nivolumab plus ipilimumab (60.0% (12/20) and 45.0% (9/20) versus 77.3% (17/22), respectively). Tobemstomig demonstrated improved safety versus nivolumab plus ipilimumab, with 2.5% (1/40) and 22.7% (5/22) of patients experiencing grade 3 or higher treatment-rela...