A Study to Compare Tivozanib Hydrochloride to Sorafenib in Participants With Refractory Advanced Renal Cell Carcinoma (RCC)
Summary
This is a Phase 3, open-label, randomized, controlled, multi-national, multi-center, parallel-arm study comparing tivozanib to sorafenib in participants with refractory advanced renal cell carcinoma (RCC). Participants will be randomized (1:1) to treatment with tivozanib or sorafenib. Participants will be stratified by International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) risk category (favorable; intermediate; poor) and prior therapy (two prior vascular endothelial growth factor receptor tyrosine kinase inhibitors (VEGFR TKI); a prior checkpoint inhibitor \[programmed cell death -1 protein (PD-1) or PD-1 ligand (PD1-L) inhibitor\] plus a prior VEGFR TKI; a prior VEGFR TKI plus any other systemic agent). All participants will be evaluated for progression free survival, overall survival, objective response rate, and the duration of response as well as safety and tolerability. Pharmacokinetic (PK) analyses are also included in study.
Timeline
- Start
- 2016-05-24
- Primary completion
- 2018-10-04
- Completion
- 2021-06-21
Outcome
Met primary endpoint
registry analysis (superiority test); Tivozanib Hydrochloride vs Sorafenib; p = 0.0165; Hazard Ratio (HR) 0.73 (95% CI 0.56 to 0.94) NCT02627963 ↗
paper Median progression-free survival was significantly longer with tivozanib (5·6 months, 95% CI 5·29-7·33) than with sorafenib (3·9 months, 3·71-5·55; hazard ratio 0·73, 95% CI 0·56-0·94; p=0·016). PMID 31810797 ↗
release “with the TIVO-3 trial demonstrating a significant PFS benefit and a favorable tolerability profile” aveooncology.com ↗
release “The presentation noted that the TIVO-3 trial met its primary endpoint of demonstrating a statistically significant benefit in median progression-free survival (PFS).” aveooncology.com ↗
release “TIVO-3 represents the first study to demonstrate a superior progression free survival (PFS) benefit versus an active comparator” aveooncology.com ↗
release “Statistically significant improvements favoring tivozanib were reported for the primary endpoint of PFS (HR=0.73; p=0.0165)” aveooncology.com ↗
release “TIVO-3 represents the first positive Phase 3 superiority study designed to help guide treatment decisions in third and fourth line RCC” aveooncology.com ↗
release “As previously announced, the TIVO-3 trial met the primary endpoint of progression free survival (PFS)” aveooncology.com ↗
Publications
- Beckermann KE, Asnis-Alibozek AG, Atkins MB, Escudier B, Hutson TE, Kasturi V, McDermott DF, Pal SK, Porta C, Rini BI, Verzoni E. Long-Term Survival in Patients With Relapsed/Refractory Advanced Renal Cell Carcinoma Treated With Tivozanib: Analysis of the Phase III TIVO-3 Trial. Oncologist. 2024 Mar 4;29(3):254-262. doi: 10.1093/oncolo/oyad348.
- Meza L, McDermott DF, Escudier B, Hutson TE, Porta C, Verzoni E, Atkins MB, Kasturi V, Pal SK, Rini B. Tivozanib in Patients with Advanced Renal Cell Carcinoma Previously Treated With Axitinib: Subgroup Analysis from TIVO-3. Oncologist. 2023 Mar 17;28(3):e167-e170. doi: 10.1093/oncolo/oyac255.
- Szarek M, Needle MN, Rini BI, Pal SK, McDermott DF, Atkins MB, Hutson TE, Escudier BJ. Q-TWiST Analysis of Tivozanib Versus Sorafenib in Patients With Advanced Renal Cell Carcinoma in the TIVO-3 Study. Clin Genitourin Cancer. 2021 Oct;19(5):468.e1-468.e5. doi: 10.1016/j.clgc.2021.03.018. Epub 2021 Apr 3.
- Rini BI, Pal SK, Escudier BJ, Atkins MB, Hutson TE, Porta C, Verzoni E, Needle MN, McDermott DF. Tivozanib versus sorafenib in patients with advanced renal cell carcinoma (TIVO-3): a phase 3, multicentre, randomised, controlled, open-label study. Lancet Oncol. 2020 Jan;21(1):95-104. doi: 10.1016/S1470-2045(19)30735-1. Epub 2019 Dec 3.
Drugs
| Evaluation | Drug | Modality | Dose | Route |
|---|---|---|---|---|
| Comparator | Sorafenib | Small molecule | 400 mg | Oral |
| Subject | Tivozanib | Small molecule | 1.5 mg | Oral |