A randomized, nivolumab-controlled, phase 2 and biomarker study of lomvastomig and tobemstomig in advanced or metastatic squamous cell carcinoma of the esophagus
Document Type
Article
Department
Haematology and Oncology, East Africa
Abstract
Purpose: The bispecific antibodies lomvastomig and tobemstomig block the immune checkpoint receptor PD-1 and either TIM-3 or LAG-3, respectively. This phase 2 study assessed their efficacy compared with nivolumab in CPI-naïve patients with unresectable advanced or recurrent ESCC who were refractory or intolerant to one prior line of chemotherapy.
Patients and Methods: This active-controlled, blinded, multicenter study randomized patients (1:1:1) to treatment with lomvastomig (2100 mg Q2W), tobemstomig (2100 mg Q2W), or nivolumab (240 mg Q2W). The primary endpoint was overall survival, secondary endpoints included objective response, progression-free survival, pharmacodynamic changes, safety/tolerability, immunogenicity, and pharmacokinetics.
Results: 190 patients were randomized, 27 to lomvastomig (this group was discontinued early), 82 to tobemstomig, and 81 to nivolumab. The median overall survival was lower in the lomvastomig (4.8 months; 80%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, 6.7-9.0). The objective response rate was 3.7%, 9.8%, and 8.6%, respectively. An exploratory biomarker analysis of tobemstomig-treated patients showed improved survival in the PD‑L1‑high (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 effects profiles.
Conclusions: Neither lomvastomig nor tobemstomig improved survival compared to nivolumab in the overall patient population. However, in the PD-L1-high (CPS≥10) and PD-L1-high/LAG3-high subgroups, tobemstomig was associated with prolonged survival, supporting PD-L1-guided treatment selection for tobemstomig in ESCC.
Publication (Name of Journal)
Clinical Cancer Research
DOI
10.1158/1078-0432.CCR-26-0851
Recommended Citation
Wyrwicz, L.,
Dechaphunkul, A.,
Lee, J.,
Turpin, A.,
Sultanbaev, A.,
Hong, M.,
Fouchardière, C.,
Alsina, M.,
Sauri, T.,
Saleh, M.
(2026). A randomized, nivolumab-controlled, phase 2 and biomarker study of lomvastomig and tobemstomig in advanced or metastatic squamous cell carcinoma of the esophagus. Clinical Cancer Research.
Available at:
https://ecommons.aku.edu/eastafrica_fhs_mc_haematol_oncol/167