Tivopath tivozanib: Phase III final data

Final data from the open-label, international Phase III TIVO-1 trial in 517 patients with advanced RCC showed that once-daily 1.5 mg oral tivozanib missed the secondary endpoint of improving median OS vs. Nexavar sorafenib (28.8 vs. 29.3 months, HR=1.245, 95% CI: 0.954, 1.624, p=0.105). Patients randomized to the Nexavar arm were eligible to cross over to receive tivozanib after radiographic confirmation of disease progression, while no crossover protocol was available for patients randomized to tivozanib. Aveo said it believes that the "high" rate of utilization of second-line anti-VEGF therapy in patients following disease progression on Nexavar impacted the OS outcome. Of patients who discontinued their initial therapy, 10% in the tivozanib arm (n=189) received subsequent anti-VEGF therapy compared to 70% in the Nexavar arm (n=226). Of the 158 patients in the Nexavar arm who received subsequent anti-VEGF therapy, 156 received tivozanib. Data were presented at the American Society of Clinical Oncology Genitourinary Cancers Symposium in Orlando. Aveo also reported data from the open-label Phase III Protocol AV-951-09-301 extension trial of patients from TIVO-1 who crossed over to receive tivozanib following progression on Nexavar showing that tivozanib led to a median OS of 19.6 months, median PFS of 8.4 months and an ORR of 13%.

Last year, Aveo reported that tivozanib met the primary endpoint of improving median PFS (11.9 vs. 9.1 months, p=0.042) and the secondary endpoint of improving ORR (33% vs. 23%, p=0.014) vs. Nexavar in the TIVO-1 trial (see BioCentury, Jan. 9, 2012 & May 28, 2012). An NDA for tivozanib is under FDA review to treat RCC, with a July 28 PDUFA date. Aveo said the OS data are included in the NDA submission. Last August, FDA expressed concerns about the OS trend in TIVO-1. At the time, the company said the estimated 1-year survival rate was 77% in the tivozanib arm compared to 81% in the Nexavar arm. ...