A randomised, open-label, phase II study of tobemstomig combinations in patients with previously untreated advanced clear-cell renal cell carcinoma.

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.