On October 1, 2018 AVEO Oncology (NASDAQ: AVEO) reported that it has initiated topline analysis of the phase 3 TIVO-3 clinical trial on the unanimous recommendation of the independent TIVO-3 Study Steering Committee, and after notice to the FDA (Press release, AVEO, OCT 1, 2018, View Source [SID1234529690]). The TIVO-3 trial is 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). The Company expects to complete data analysis and report topline results from the study in approximately 6 weeks.
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The Steering Committee recommendation was preceded by a slowing in the rate of progression free survival (PFS) events in the trial over the last 4-6 months. The reasons given by the Steering Committee for the unanimous recommendation were that current patients have been on study for at least one year and may not progress for some time, and that the small reduction in events at the time of final analysis was unlikely to materially affect the clinical interpretation of the results. As of September 26, 2018, the last review of events, a total of 242 PFS events had occurred in the trial. The Company plans to set the data cutoff date for the primary analysis at October 4, 2018. Performing the primary analysis at 242 events reduces the power of the study from 90% (based on the prior target of 255 PFS events) to 88%.
Following the last review of events, 42 patients remain on treatment in the TIVO-3 study with 28 of the remaining patients yet to have a PFS event as determined by the independent radiology committee. All patients still enrolled in the study will continue to receive treatment per study protocol. The Company will remain blinded to study data until data analysis is complete.
"Initiation of the topline analysis of the TIVO-3 trial brings us one step closer to potentially realizing the strategy we laid out in 2015, which included commercialization of tivozanib in the United States and Europe, and exploration of tivozanib’s clinical potential in immunotherapy combinations," said Michael Bailey, president and chief executive officer of AVEO. "With the introduction of immunotherapy as a treatment for earlier-line RCC, survival among patients is extending well beyond disease progression on first- and second-line treatment, which we believe may substantially increase the third-plus-line opportunity for tivozanib. TIVO-3 has the potential to serve as the first prospective Phase 3 randomized dataset in this setting, creating an evidence-based guidepost for sequencing therapies in refractory disease. We look forward to announcing the topline results of TIVO-3 in the coming weeks."
The TIVO-3 trial was designed to enroll patients with RCC who have failed at least two prior regimens, including VEGFR-TKI therapy. 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 PFS. Secondary endpoints include overall survival (OS), overall response rate, and safety and tolerability. TIVO-3, together with the previously completed TIVO-1 trial of tivozanib in the first-line treatment of RCC, is designed to support a regulatory submission of tivozanib in the U.S. as a treatment for RCC, if the data are positive. TIVO-3 patients were exclusively enrolled in North America, Western Europe, and Central Europe.
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 (RCC) 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.1,2 Tivozanib has been shown to significantly reduce regulatory T-cell production in preclinical models, enabling potentially enhanced activity when used in combination with immune modulating therapy.3 As part of a North American registration plan, tivozanib is currently being studied in the Phase 3 TIVO-3 trial, a randomized, controlled, multi-center, open-label study to compare tivozanib to sorafenib in subjects with refractory RCC. Tivozanib has been investigated in several tumors types, including renal cell, hepatocellular, colorectal and breast cancers.