Data from Pharmawand - Curated by EPG Health - Date added 11 September 2019
AVEO Oncology announced results from the second prespecified analysis of overall survival (OS) in the TIVO-3 trial comparing Fotivda (tivozanib) to sorafenib in 350 subjects with highly refractory metastatic renal cell carcinoma (RCC). TIVO-3 is the Company’s Phase III randomized, controlled, multi-center, open-label study. These results include an OS hazard ratio (HR) below 1.00, favoring tivozanib (HR=0.99; 95% CI: 0.76-1.29; p=0.95). An OS hazard ratio assesses the relative risk of death for the entirety of the data set. TIVO-3 is the first and only positive Phase III study in 3rd and 4th line RCC, and the first Phase III study in RCC to investigate a predefined subpopulation of patients who received prior immunotherapy, an emerging standard of care for earlier lines of therapy.
The data cutoff date for the second prespecified analysis was August 15, 2019, two years from the last patient enrolled and approximately ten months from the data cut-off date for the first prespecified analysis. Between the two data cut-off dates, 16 additional OS events were reported on the tivozanib arm and 28 on the sorafenib arm, resulting in a total of 114 OS events on the tivozanib arm and 113 on the sorafenib arm. Median OS, a point in time value separating the earlier half of events from the latter half within each arm, was 16.4 months for tivozanib (95% CI: 13.4-22.2) and 19.7 months for sorafenib (95% CI: 15.0-24.2). Twenty patients remain progression free on the tivozanib arm and two on the sorafenib arm, with a median duration on study of 32.5 months. Statistically significant improvements favoring tivozanib were reported for PFS (HR=0.73; p=0.0165) and ORR (18% vs. 8%; p=0.02).
The Company also announced that tivozanib was found to be generally well-tolerated, with grade 3 or higher adverse events consistent with those observed in previous tivozanib trials. Infrequent but severe adverse events reported in greater number in the tivozanib arm were thrombotic events similar to those observed in previous tivozanib studies. The most common adverse event in patients receiving tivozanib was hypertension, an adverse event known to reflect effective VEGF pathway inhibition. The Company plans to discuss the updated OS results with the FDA to identify the appropriate path forward for tivozanib in RCC in the fourth quarter, and to provide an update regarding the potential submission of a New Drug Application for tivozanib in RCC following these discussions.