Phase 3 Study Update of Tivozanib for First-Line Advanced Renal Cell Carcinoma

AVEO and Astellas announced detailed data from TIVO-1 (Tivozanib Versus Sorafenib in 1st line Advanced Renal Cell Carcionma [RCC]).

TIVO-1 was a global, randomized Phase 3 superiority clinical trial evaluating the efficacy and safety of investigational drug tivozanib compared to sorafenib (Nexavar; Bayer and Onyx) in 517 patients with advanced renal cell carcinoma (RCC). Patients randomized to the sorafenib arm of TIVO-1 were eligible to cross over to tivozanib therapy under a separate protocol after radiographic confirmation of disease progression. No crossover protocol was available for patients randomized to the tivozanib arm.

Key data from TIVO-1 include:

  • Based on independent radiological reviews, tivozanib demonstrated a statistically significant improvement in PFS with a median PFS of 11.9 months compared to a median PFS of 9.1 months for sorafenib in the overall (Intent To Treat) study population (HR=0.797, 95% CI 0.639–0.993; P=0.042). Objective response rate (ORR) for tivozanib was 33% compared to 23% for sorafenib (P=0.014). The efficacy advantage of tivozanib over sorafenib was consistent across subgroups in the study.
  • In patients who were treatment naïve for advanced RCC (70% of total study population), tivozanib demonstrated a statistically significant improvement in PFS with a median PFS of 12.7 months compared to a median PFS of 9.1 months for sorafenib (HR 0.756, 95% CI 0.580–0.985; P=0.037). This is the longest median PFS reported to date in treatment naïve advanced RCC patients in a pivotal study.
    • In the subpopulation of patients who were pretreated with systemic therapy including cytokines (30% of total study population), tivozanib demonstrated an improvement in PFS with a median PFS of 11.9 months compared to a median PFS of 9.1 months for sorafenib.

Overall survival (OS) data are not yet mature. In TIVO-1, 53% of patients randomized to the sorafenib arm of the trial went on to receive subsequent therapy, nearly all of whom received tivozanib after sorafenib. Based on an early, interim analysis, 81% of these patients achieved one year OS. In comparison, only 17% of patients randomized to tivozanib went on to receive a subsequent therapy, and 77% of these patients achieved one year OS.

Tivozanib is a potent, selective, and continuous inhibitor of all three vascular endothelial growth factor (VEGF) receptors that is designed to optimize VEGF blockade while minimizing off-target toxicities.

For more information, call (617) 299-5000 or visit www.aveopharma.com.