Overview of tivozanib (tivo) safety in phase 3 clinical trials in patients with metastatic renal cell carcinoma (mRCC)
Recommended Citation
Barata PC, Rini B, Choueri T, Pal S, Barthelemy P, Iacovelli R, McGregor BA, Albiges L, Molina-Cerrillo J, Garmezy B, Hauke R, Tejwani S, Basu A, Moon H, Beckermann K, Ornstein M, McKay R, Lebedinsky C, Braendle EE, Motzer R. Overview of tivozanib (tivo) safety in phase 3 clinical trials in patients with metastatic renal cell carcinoma (mRCC). 2025; (S2).
Document Type
Conference Proceeding
Publication Date
10-9-2025
Abstract
Background: Tivo is a potent and highly selective VEGFR inhibitor designed to optimize VEGF blockade and minimize off-target toxicities. In TiNivo-2, patients with mRCC who had previous exposure to ICI, were randomized to receive study treatment as 2L or 3L with Tivo alone at 1.34mg, or at 0.89mg in combination with the ICI nivolumab (nivo).[1] The addition of nivo to tivo in second line (2L) or third-line treatment (3L) did not improve outcomes, and tivo monotherapy showed activity as a 2L treatment in the post ICI setting. In TIVO-3, randomized patients had at least two previous systemic treatments and received tivo or sorafenib. We carried out a safety review of tivoza - nib monotherapy in these 2 randomized trials in the context of popu - lations that had been previously exposed to VEGFR-TKI and ICI treatment. Methods: The safety profile of tivo monotherapy was evaluated in these two phase 3 trial cohorts that consisted of the tivo monotherapy arms of TiNivo-2 (N =171), and TIVO-3 (N =173).[2] Results: Patient baseline characteristics of the two tivo monotherapy cohorts showed some differences, most notably in the distribution of previous exposure to VEGFR target therapy and ICIs: in TIVO-3, exposure to two prior VEGFR-TKI was 45%, to prior ICI plus VEGFR-TKI was 27%, and to a prior VEGFR-TKI plus other agent was 28%. Whereas inTiNivo-2, exposure to prior ICI was 100% (71% as the most recent line of therapy), while exposure to VEGFR-TKI was: none 31%, one 56% and two 13%. Additionally, 94% of TIVO-3 participants were white, compared with 62% of those in TiNivo-2. The incidence of grade 3-4 TEAEs and serious AEs was lower in TiNivo-2, however there was consistency in the incidence of any cause TEAEs, as well as those leading to death or treatment modifications in both cohorts (Table 1). For TEAEs ≥ Grade 3, hypertension was the most common, occurring in approximately 20% of patients in each cohort; while the incidence of all other TEAEs ≥ Grade 3 was lower, they also occurred at similar rates in each cohort (Table 1). Conclusions: Here, results show that tivo has a manageable safety profile across phase 3 trials. The better tolerability of tivo in the TiNivo-2 study vs TIVO-3 is driven in part by more patients enrolled in the earlier lines of treatment (2L).
Issue
S2
