On February 16, 2019 AVEO Oncology (NASDAQ:AVEO) reported the presentation of data from the Phase 3 TIVO-3 study of tivozanib (FOTIVDA) versus sorafenib in refractory advanced or metastatic renal cell carcinoma (RCC) (Press release, AVEO, FEB 16, 2019, View Source [SID1234533366]). The data were presented by Brian Rini, MD, Professor of Medicine, Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, and Director, Cleveland Clinic Genitourinary Cancer Program, during an oral presentation titled, "TIVO-3: A Phase 3, Randomized, Controlled, Multi-Center, Open-Label Study to Compare Tivozanib to Sorafenib in Subjects with Refractory Advanced Renal Cell Carcinoma (RCC)" at the 2019 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Genitourinary (GU) Cancers Symposium held February 14-16, 2019 in San Francisco. A copy of the presentation will be available in the Publications & Presentation section of the Company’s website.
Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:
Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing
Schedule Your 30 min Free Demo!
"Tivozanib continues to demonstrate a unique activity and tolerability profile among VEGF TKIs in the treatment of kidney cancer," said Dr. Rini. "This is underscored by a significant improvement in progression free survival and overall response rate compared to sorafenib in patients with treatment-refractory advanced RCC. I look forward to understanding how this improvement impacts overall survival as the TIVO-3 study continues to mature."
"We remain committed to our goal of improving outcomes and patient experience in RCC," said Michael Bailey, president and chief executive officer of AVEO. "The improvement in progression free survival in the TIVO-3 study, particularly in patients who received prior immunotherapy, is noteworthy. We are hopeful that these positive PFS outcomes translate into an improved overall survival hazard ratio when we report a more mature interim OS outcome in the fourth quarter of 2019. We expect to make a new drug application filing decision following the availability of more mature OS results."
TIVO-3 Topline Study Results
The TIVO-3 trial is a Phase 3 randomized, controlled, multi-center, open-label study designed to compare tivozanib (FOTIVDA) to sorafenib in 350 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 the risk of progression or death (Hazard Ratio [HR]=0.74, p=0.02, see Figure 1). 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 (CPI) therapy in earlier lines of treatment. PFS for tivozanib was longer than sorafenib both in patients who received prior CPI therapy and those who received two prior VEGF TKI therapies. Patients who received prior CPI therapy had a median PFS of 7.3 months with tivozanib and 5.1 months with sorafenib (HR=0.55, p=0.03, see Figure 2). One- and two-year PFS in patients who received tivozanib following CPI therapy was 35% and 25%, respectively, and 4% and n/a for patients receiving sorafenib following CPI therapy at those respective time periods.
The secondary endpoint of overall response rate for patients receiving tivozanib was 18% compared to 8% for patients receiving sorafenib (p=0.02). Median duration of response (DOR) in patients receiving tivozanib was not reached (95% CI:12.9,—) and was 5.7 months for patients receiving sorafenib (95% CI:5.6,—). DOR probability at 1 year was 71% and 46% for tivozanib and sorafenib, respectively, and 55% and 0% at two years.
The analysis of the secondary endpoint of overall survival (OS) was not mature at the time of the final PFS analysis, and currently reflects ~50% of potential OS events. As previously disclosed, the updated preliminary OS analysis conducted at an October 4, 2018 data cutoff date, which included additional patients previously lost to follow-up, showed a non-statistically significant difference in OS favoring sorafenib (HR=1.12, p=0.44). The Company intends to conduct an additional interim OS analysis in August 2019, the results of which are expected to be reported in the fourth quarter of 2019.
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.
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 models3, and has demonstrated synergy in combination with nivolumab (anti PD-1) in a Phase 2 study in RCC. Tivozanib has been investigated in several tumor types, including renal cell, hepatocellular, colorectal and breast cancers.