Tivozanib (VEGFR TKI) Beats Tivozanib+Nivolumab in Post-ICI mRCC PFS (No OS Gain)

Tivozanib (Tivo) is an oral, selective VEGFR tyrosine kinase inhibitor; TiNivo-2 (Phase 3; NCT04987203) tested ICI rechallenge by adding nivolumab (anti–PD-1) to tivozanib versus tivozanib alone in metastatic RCC after prior ICI (data cutoff October 17, 2025; treated n=171 Tivo vs n=168 Tivo/Nivo; median follow-up 28.4 vs 27.2 months). At final analysis, efficacy was essentially flat in the ITT population (mPFS 7.43 vs 5.72 months; HR 0.96) and there was no mOS separation (22.93 vs 23.85 months; HR 0.95), while the 2L subgroup numerically favored tivozanib monotherapy (mPFS 9.23 vs 5.95 months). Grade ≥3 hypertension was common and similar (22.8% vs 22.6%), with low rates of grade ≥3 diarrhea (2.3% vs 3.6%) and PPE (0.6% vs 1.2%); treatment-related SAEs were 8.8% vs 10.7%—a tolerability profile broadly in-family for VEGFR TKIs and not clearly better than common post-IO benchmarks like cabozantinib in METEOR (mPFS ~7.4 months; mOS ~21.4 months) or lenvatinib+everolimus (mPFS 14.6 months, albeit from a Phase 2 trial in a different treatment era/population).