A randomised, open-label, phase II study of tobemstomig combinations in patients with previously untreated advanced clear-cell renal cell carcinoma
Year: 2026
Type: article
Study designs: Randomized Controlled Trial, Clinical Trial
Abstract: BACKGROUND: Immune checkpoint inhibitors combined with vascular endothelial growth factor (VEGF)-targeted tyrosine kinase inhibitors (TKIs) have improved advanced renal cell carcinoma (RCC) outcomes, yet median progression-free survival (PFS) remains <2 years. PATIENTS AND METHODS: This randomised (1 : 1 : 1), open-label, phase II study (NCT05805501) evaluated tobemstomig [bispecific anti-programmed cell death protein 1 (PD-1)/lymphocyte-activation gene 3] plus axitinib (VEGF-TKI) and tobemstomig plus tiragolumab (anti-T-cell immunoreceptor with immunoglobulin and immunoreceptor tyrosine-based inhibition motif domains) plus axitinib versus pembrolizumab (anti-PD-1) plus axitinib (control) in patients with untreated, locally advanced unresectable/metastatic clear-cell RCC with intermediate/poor International Metastatic Renal Cell Carcinoma Database Consortium risk. Following a protocol-specified interim futility analysis that led to study termination, the primary endpoint was amended from PFS and incidence/severity of adverse events (AEs) to the latter only. Efficacy was evaluated descriptively. RESULTS: In the safety population (198 patients: tobemstomig-axitinib, n = 66; tobemstomig-tiragolumab-axitinib, n = 65; control, n = 67), grade 3-4 AEs occurred in 62.1%, 67.7% and 56.7% of patients in the respective arms and treatment-related serious AEs occurred in 22.7%, 29.2% and 13.4%. Confirmed overall response rates were 51.5%, 53.8% and 51.5%; median PFS was 12.4 [95% confidence interval (CI) 8.4-16.3], 12.5 (95% CI 7.3-17.2) and 12.5 months (95% CI 9.5 to not estimable). CONCLUSIONS: Tobemstomig-containing regimens were associated with increased toxicity and did not demonstrate meaningful efficacy improvement relative to control.
Source: ESMO Open
Institutions: Vanderbilt University, Vanderbilt-Ingram Cancer Center, Queen Mary University of London, Barts Health NHS Trust, Poznan University of Medical Sciences, Yonsei University, Yonsei University Health System, Yonsei Cancer Hospital, Peking University Cancer Hospital, Instituto Ramón y Cajal de Investigación Sanitaria, Centro de Investigación Biomédica en Red de Cáncer, Hospital Universitario Ramón y Cajal, Tianjin Medical University Cancer Institute and Hospital, Asan Medical Center, University of Ulsan, Jagiellonian University, Hospital Clínico San Carlos, University of Alabama at Birmingham, University of California, Irvine, Roche (United Kingdom), Roche (Canada), Genentech, Institut Gustave Roussy
Language: English
Subfield: Pulmonary and Respiratory Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $3,910
Funders: Pfizer, Roche, F. Hoffmann-La Roche
OpenAlex ID: W7220936520