A Randomized, Nivolumab-Controlled, Phase II Biomarker Study of Lomvastomig and Tobemstomig in Advanced or Metastatic Squamous Cell Carcinoma of the Esophagus.
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Wyrwicz Lucjan, Dechaphunkul Arunee, Lee Jong-Seok, Turpin Anthony, Sultanbaev Aleksandr, Hong Min Hee, De La Fouchardière Christelle, Alsina Maria, Sauri Tamara, Asirwa Fredrick, Pernot Simon, Cho Sanghee, Saleh Mansoor, Bergamo Francesca, Cohen Romain, Baeksgaard Lene, Lordick Florian, Kraus Dominik, Heichinger Christian, Tran Vu-Long, Mücke Merlind, Michielin Francesca, McIntyre Christine, Madden-Raja Kate, Marbach Daniel, Davydov Iakov I, Lopes Rui, Wilson Sabine, Rutishauser Tobias, Codarri Deak Laura, Kao Henry, Markert Christoph, Kim Sung-Bae
Аннотация
PATIENTS AND METHODS: This active-controlled, blinded, multicenter study randomized patients (1:1:1) to treatment with lomvastomig (2,100 mg once every 2 weeks), tobemstomig (2,100 mg once every 2 weeks), or nivolumab (240 mg once every 2 weeks). The primary endpoint was overall survival (OS); secondary endpoints included objective response, progression-free survival, pharmacodynamic changes, safety/tolerability, immunogenicity, and pharmacokinetics.
RESULTS: A total of 190 patients were randomized: 27 to lomvastomig (this group was discontinued early), 82 to tobemstomig, and 81 to nivolumab. The median OS was lower in the lomvastomig [4.8 months; 80% confidence interval (CI), 2.8-5.8] and tobemstomig (6.7 months; 80% CI, 5.4-8.7) arms than in the nivolumab arm (8.1 months; 80% CI, 6.7-9). The objective response rates were 3.7%, 9.8%, and 8.6%, respectively. An exploratory biomarker analysis of tobemstomig-treated patients showed improved survival in the PD-L1-high [combined positive score (CPS) ≥ 10] versus the PD-L1-low (CPS < 10) subgroup, with the greatest benefit in patients with concurrent high expression of PD-L1 and LAG-3 (>median). Adverse events with lomvastomig and tobemstomig were manageable, and the safety profiles of all three compounds remained consistent with their known immune-mediated side effect profiles.
CONCLUSIONS: Neither lomvastomig nor tobemstomig improved survival compared with nivolumab in the overall patient population. However, in the PD-L1-high (CPS ≥ 10) and PD-L1-high/LAG-3-high subgroups, tobemstomig was associated with prolonged survival, supporting PD-L1-guided treatment selection for tobemstomig in ESCC.