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AVEO Oncology (AVEO) Reports Updated Overall Survival Hazard Ratio of 0.99 in Phase 3 TIVO-3 Trial of Tivozanib in Renal Cell Carcinoma

September 10, 2019 6:31 AM EDT

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AVEO Oncology (NASDAQ: AVEO) today announced results from the second prespecified analysis of overall survival (OS) in the TIVO-3 trial. TIVO-3 is the Company’s Phase 3 randomized, controlled, multi-center, open-label study to compare tivozanib (FOTIVDA®) to sorafenib in 350 subjects with highly refractory metastatic renal cell carcinoma (RCC). These results include an OS hazard ratio (HR) below 1.00, favoring tivozanib (HR=0.99; 95% CI: 0.76-1.29; p=0.95). An OS hazard ratio assesses the relative risk of death for the entirety of the data set. TIVO-3 is the first and only positive Phase 3 study in 3rd and 4th line RCC, and the first Phase 3 study in RCC to investigate a predefined subpopulation of patients who received prior immunotherapy, an emerging standard of care for earlier lines of therapy.

The data cutoff date for the second prespecified analysis was August 15, 2019, two years from the last patient enrolled and approximately ten months from the data cut-off date for the first prespecified analysis. Between the two data cut-off dates, 16 additional OS events were reported on the tivozanib arm and 28 on the sorafenib arm, resulting in a total of 114 OS events on the tivozanib arm and 113 on the sorafenib arm. Median OS, a point in time value separating the earlier half of events from the latter half within each arm, was 16.4 months for tivozanib (95% CI: 13.4-22.2) and 19.7 months for sorafenib (95% CI: 15.0-24.2). Twenty patients remain progression free on the tivozanib arm and two on the sorafenib arm, with a median duration on study of 32.5 months.

In November 2018, the Company announced positive final results for the primary endpoint of progression-free survival (PFS) and the secondary endpoint of overall response rate (ORR). Statistically significant improvements favoring tivozanib were reported for PFS (HR=0.73; p=0.0165) and ORR (18% vs. 8%; p=0.02). The Company also announced that tivozanib was found to be 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.

The Company plans to discuss the updated OS results with the U.S. Food and Drug Administration to identify the appropriate path forward for tivozanib in RCC in the fourth quarter, and to provide an update regarding the potential submission of a New Drug Application for tivozanib in RCC following these discussions.

“These are the first data to demonstrate durable improvements in this highly refractory advanced kidney cancer population, including the post-immunotherapy setting, a predefined subset of the TIVO-3 trial,” said Brian Rini, MD, Professor of Medicine, Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Director, Cleveland Clinic Genitourinary Cancer Program, and principal investigator of the TIVO-3 trial. “The TIVO-3 study suggests the potential for tivozanib to serve as an important new treatment option for patients with advanced RCC. I look forward to seeing tivozanib studied further in the immunotherapy combination setting, and to continuing to explore its full potential in the evolving RCC treatment landscape.”

“We are pleased to see that the positive PFS and ORR outcomes from TIVO-3 have translated into an improved OS hazard ratio,” said Michael Bailey, president and chief executive officer of AVEO. “On behalf of the entire AVEO team, we once again offer our sincerest thanks to the patients, caregivers and investigators for participating in this study. AVEO remains committed to improving outcomes for patients with RCC, and we look forward to discussing these results with the FDA.”

Conference Call and Webcast

In connection with this announcement, AVEO will host a conference call and audio webcast today, September 10, 2019, at 8:00 am Eastern Time. The call can be accessed by dialing (844) 882-7841 (U.S. and Canada) or (574) 990-9828 (international). The passcode for the conference call is 3275406. To access the live audio webcast, or the subsequent archived recording, please visit the Investors section of the AVEO website at www.aveooncology.com. The webcast will be recorded and available for replay on AVEO’s website for two weeks.

About TIVO-3

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 were randomized 1:1 to receive either tivozanib or sorafenib, with no crossover between arms. The primary endpoint of the study is progression free survival (PFS). Secondary endpoints include overall survival (OS), overall response rate (ORR), 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 in multiple lines of therapy. 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 Kirin and approved for the treatment of adult patients with advanced renal cell carcinoma (RCC) in the European Union plus Norway, New Zealand 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 models3 and has demonstrated synergy in combination with nivolumab (anti PD-1) in a Phase 2 study in RCC4. Tivozanib has been investigated in several tumor types, including renal cell, hepatocellular, colorectal, ovarian and breast cancers.



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