Long, Georgina V. and Nair, Nitya and Marbach, Daniel and Scolyer, Richard A. and Wilson, Sabine and Cotting, Denise and Staedler, Nicolas and Amaria, Rodabe N. and Ascierto, Paolo Antonio and Tarhini, Ahmad A. and Robert, Caroline and Hamid, Omid and Gaudy-Marqueste, Caroline and Lebbe, Celeste and Munoz-Couselo, Eva and Menzies, Alexander M. and Pages, Cecile and Curigliano, Giuseppe and Mandala, Mario and Jessop, Nikki and Bader, Uwe and Perdicchio, Maurizio and Teichgraber, Volker and Muecke, Merlind and Markert, Christoph and Blank, Christian (2025) 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. NATURE MEDICINE, 31 (11). ISSN 1078-8956, 1546-170X
Full text not available from this repository. (Request a copy)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-related adverse events (TRAEs), respectively, and 0% (0/40) and 13.6% (3/22) of patients discontinuing treatment due to TRAEs, respectively. Grade 3 or higher TRAEs were reported by 15% (3/20) of patients in the tobemstomig plus tiragolumab arm and by no patients in the atezolizumab plus tiragolumab arm. Baseline CD8+ and CD3+ tumor-infiltrating T cell density, IFN gamma pathway and effector T cell gene expression, tumor mutational burden and pre-surgery circulating tumor DNA correlated with pathological response across treatments. In conclusion, in the Morpheus-Melanoma study, tobemstomig demonstrated a similar pathological response and improved safety profile versus nivolumab plus ipilimumab in patients with resectable stage III melanoma. ClinicalTrials.gov identifier: NCT05116202.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | STAGE-III; NIVOLUMAB; SURVIVAL; ADJUVANT; PEMBROLIZUMAB; RELATLIMAB; |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Hals-Nasen-Ohren-Heilkunde |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 27 Mar 2026 08:25 |
| Last Modified: | 27 Mar 2026 08:25 |
| URI: | https://pred.uni-regensburg.de/id/eprint/67942 |
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