On October 5, 2017 AVEO Oncology (NASDAQ:AVEO) reported the completion of a pre-planned futility analysis of the Phase 3 TIVO-3 trial, the Company’s randomized, controlled, multi-center, open-label study to compare FOTIVDA (tivozanib) to sorafenib in subjects with refractory advanced renal cell carcinoma (RCC) (Press release, AVEO, OCT 5, 2017, View Source [SID1234520798]). Based on the results of the futility analysis, which was reviewed by an independent statistician, the study will continue as planned without modification. This analysis did not allow for early stopping due to efficacy to assure adequate follow-up for the key secondary endpoint of overall survival. The pre-planned futility analysis was triggered by the reporting of 128 progression events in early August. Additional events were recorded as part of the data management process leading into the futility analysis, resulting in a revised data cut-off date for the analysis of May 29. The Company continues to expect the TIVO-3 to read out in the first quarter of 2018.
The TIVO-3 trial, together with the previously completed TIVO-1 trial of tivozanib in the first line treatment of RCC, is designed to support regulatory approval of tivozanib in the U.S. as a first and third line treatment for RCC.
“The treatment of advanced renal cell cancer is undergoing rapid change, with immunotherapy and combination regimens delivering improved outcomes for patients and shaping a new treatment paradigm,” said Michael Bailey, president and chief executive officer of AVEO. “We believe our tivozanib clinical strategy positions us well in this evolving landscape, with the TIVO-3 study on track to provide the first post-immunotherapy pivotal datasets for a VEGF-TKI, and the TiNivo study providing early and encouraging combination data. We look forward to readout of the TIVO-3 trial in the first quarter of 2018. We also look forward to presenting Phase 1 results from the Phase 1/2 TiNivo study of tivozanib in combination with OPDIVO at a medical conference this fall, and to leveraging tivozanib’s unique safety and efficacy profile in future potential therapy combinations.”
The TIVO-3 trial was designed to enroll patients with recurrent RCC who have failed at least two prior regimens, including VEGFR-TKI therapy (other than sorafenib). Eligible patients may also have received checkpoint inhibitor therapy in earlier lines of treatment. Patients are randomized 1:1 to receive either tivozanib or sorafenib, with no crossover between arms. The primary endpoint of the study is progression free survival. Secondary endpoints include overall survival, overall response rate, and safety and tolerability.
The TiNivo trial is a Phase 1/2 study of tivozanib in combination with Bristol-Myers Squibb’s OPDIVO (nivolumab), an immune checkpoint, or PD-1, inhibitor, for the treatment of RCC. The TiNivo trial is being led by the Institut Gustave Roussy in Paris under the direction of Bernard Escudier, MD, Chairman of the Genitourinary Oncology Committee. The trial advanced into the Phase 2 expansion portion following successful completion of the Phase 1 dose escalation portion. The combination was well tolerated to the full dose and schedule of single agent tivozanib, with no dose limiting toxicities. The expansion portion of the trial is expected to enroll an additional 20 subjects. Phase 1 results from the ongoing study have been submitted for presentation at a scientific meeting taking place in the fourth quarter.
About Tivozanib (FOTIVDA)
Tivozanib (FOTIVDA) is an oral, once-daily, vascular endothelial growth factor (VEGF) tyrosine kinase inhibitor (TKI) discovered by Kyowa Hakko Kirin and approved for the treatment of adult patients with advanced renal cell carcinoma in the European Union plus Norway and Iceland. It is a potent, selective and long half-life inhibitor of all three VEGF receptors and is designed to optimize VEGF blockade while minimizing off-target toxicities, potentially resulting in improved efficacy and minimal dose modifications. Tivozanib has been investigated in several tumors types, including renal cell, colorectal and breast cancers.