AVEO’s RCC Drug Hits the Mark in Phase III Trial

Microscopic image of clear cell carcinoma, the most common type of renal cell carcinoma.

Cambridge, Mass.-based AVEO Oncology hit the mark in its Phase III study of a treatment for highly refractory advanced or metastatic renal cell carcinoma (RCC). The company said its drug tivozanib met its primary endpoint of demonstrating a statistically significant benefit in progression-free survival (PFS).

AVEO’s tivozanib is an oral, once-daily, vascular endothelial growth factor (VEGF) tyrosine kinase inhibitor. In the Phase III TIVO-3 trial, the company compared tivozanib to sorafenib in 351 patients with the RCC indication. AVEO said tivozanib demonstrated a 44 percent improvement in median PFS and 26 percent reduction in risk of progression or death in dosed patients. Median progression-free survival was 5.6 months for tivozanib compared to 3.9 months for sorafenib, the company said. The TIV-3 trial included patients with RCC who have failed at least two prior regimens. Among those patients who have failed the prior regimens, AVEO said approximately 26 percent 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 company noted.

In addition to the PFS data, AVEO said its analysis of the secondary endpoint for overall survival was not yet mature at the time of the final PFS analysis. AVEO said only 46 percent of potential overall survival events had been reported at that time. At the time of the preliminary OS analysis, no statistically significant difference in OS was observed, the company said. Final survival analysis is expected in August 2019, which will be two years after the final patient had been enrolled in the Phase III trial. The secondary endpoint of overall response rate for patients receiving tivozanib was 18 percent compared to 8 percent for patients receiving sorafenib, the company said. Tivozanib was generally well-tolerated, the company said.

With data from the TIVO-3 trial, as well as the previously completed Phase III TIVO-1 trial of tivozanib in the first line treatment of RCC, AVEO said it intends to submit a New Drug Application to the U.S. Food and Drug Administration (FDA) within the next six months. Tivozanib has been approved for the treatment of adult patients with advanced renal cell carcinoma (RCC) in the European Union plus Norway and Iceland. In those markets, it is sold under the brand name of Fotivda.

Brian Rini, director of the Cleveland Clinic Genitourinary Cancer Program and principal investigator of the Phase III TIVO-3 trial, said tivozanib’s therapeutic profile is distinct among VEGF TKIs as a treatment for RCC. Specifically, Rini pointed to the PFS benefit, as well as its favorable tolerability profile.

In the advanced disease setting, these outcomes are particularly meaningful, providing the first large, pivotal dataset that shows sequencing of treatment following earlier TKI and immunotherapy treatment. This profile suggests an important place for tivozanib in the evolving treatment paradigm for RCC and, taken together with early combination data, the need to study tivozanib further in combination with immunotherapies,” Rini said in a statement.