Positive Phase III TIVO-3 trial of tivozanib to treat refractory advanced or metastatic renal cell carcinoma.- Aveo Oncology.

AVEO Oncology announced positive topline results from the primary analysis of the TIVO-3 trial, the Company�s Phase III randomized, controlled, multi-center, open-label study to compare tivozanib (FOTIVDA) to sorafenib (Nexavar) in 351 subjects with highly refractory advanced or metastatic renal cell carcinoma (RCC). The trial met its primary endpoint of demonstrating a statistically significant benefit in progression-free survival (PFS).

Tivozanib demonstrated a 44% improvement in median PFS and 26% reduction in risk of progression or death (Hazard Ratio [HR]=0.74, p=0.02). Median PFS was 5.6 months for tivozanib compared to 3.9 months for sorafenib. The TIVO-3 trial enrolled patients with RCC who have failed at least two prior regimens. Among these, approximately 26% of patients received checkpoint inhibitor therapy in earlier lines of treatment. Tivozanib PFS was longer than sorafenib both in patients who received prior checkpoint inhibitor therapy and those who did not. The analysis of the secondary endpoint of overall survival (OS) was not mature at the time of the final PFS analysis, with only 46% of potential OS events having been reported. At the time of the preliminary OS analysis, no statistically significant difference in OS was observed (HR=1.06, p=0.69). The final survival analysis per protocol is planned for August 2019, two years following the last patient enrolled. Detailed results of the trial will also be submitted for presentation at an upcoming major medical meeting. The secondary endpoint of overall response rate for patients receiving tivozanib was 18% compared to 8% for patients receiving sorafenib (p=0.02). Tivozanib was 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. Based on results from the TIVO-3 trial, together with the previously completed Phase 3 TIVO-1 trial of tivozanib in the first line treatment of RCC, the Company�s goal is to submit a New Drug Application (NDA) to the U.S. Food and Drug Administration (FDA) in approximately six months.