A randomised, open-label, phase II study of tobemstomig combinations in patients with previously untreated advanced clear-cell renal cell carcinoma
In brief
Tobemstomig regimens raised serious treatment-related events to 23%-29%, without improving control
In this phase II trial, serious treatment-related side effects affected 23% to 29% of patients receiving tobemstomig combinations, versus 13% with pembrolizumab plus axitinib. Response rates were about 52% in all three groups, and median progression-free survival was about 12.5 months; the trial stopped after an interim futility analysis, with no meaningful efficacy gain to offset the added toxicity.
- Journal
- ESMO open (Q1)
- Published
- 8 October 2026
- Study design
- Phase 2 randomized trial (exploratory)
- Evidence level
- Level 2, Moderate (CEBM 2b)
- Authors
- B I Rini, T Powles, P Tomczak, S J Shin, J Guo, J Molina-Cerrillo, et al.
- PMID
- 42849355
- DOI
- 10.1016/j.esmoop.2026.108587
Why clinicians should know about it
- Picked for Oncology and Radiation Oncology (paper of the day, 9 October 2026): Phase II RCT of tobemstomig combos in RCC
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.
Abstract as published, via PubMed.
For healthcare professionals. The summary is generated by AI from the published abstract, and the evidence level is assigned automatically from the study design on the Oxford CEBM hierarchy. Neither is medical advice. Read the full paper before changing practice.