On February 12, 2020 AVEO Oncology (NASDAQ: AVEO) reported the publication of results from a monotherapy trial of tivozanib, the Company’s vascular endothelial growth factor receptor tyrosine kinase inhibitor (VEGFR-TKI), in patients with advanced, inoperable hepatocellular carcinoma (HCC) in the British Journal of Cancer (Press release, AVEO, FEB 12, 2020, View Source [SID1234554234]). The article, titled "A multicentre phase 1b/2 study of tivozanib in patients with advanced inoperable hepatocellular carcinoma," is available online first via this link.
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!
For the Phase 1b/2 tivozanib study, a total of 27 patients were enrolled. The study sought to evaluate the safety, dosing, pharmacokinetics, pharmacodynamics, and preliminary anti-tumor activity of tivozanib in patients with advanced HCC. The recommended Phase 2 dose (RP2D) was determined to be 1.0 mg once daily for 21 days followed by 7 days off treatment on a 28-day cycle. Median progression free and overall survival were 24 weeks and 9 months, respectively, for patients treated at the RP2D, with an overall response rate of 21%. A significant decrease in soluble plasma VEGFR-2 was also observed, suggesting adequate target engagement.
"HCC represents the fastest rising cause of cancer-related death in the U.S., with five-year survival at approximately 26%," said Michael Bailey, president and chief executive officer. "This study is an important steppingstone in understanding tivozanib’s safety and efficacy in HCC, and was the foundation for our ongoing Phase 1b/2 DEDUCTIVE study of tivozanib in combination with IMFINZI (durvalumab). As we work toward our expected filing of a New Drug Application with the FDA this quarter for tivozanib in kidney cancer, we look forward to expanding our tivozanib-immunotherapy clinical strategy as part of our effort to maximize its long-term potential."
Enrollment is currently underway in a Phase 1b/2 DEDUCTIVE study of tivozanib in combination with IMFINZI (durvalumab), AstraZeneca’s human monoclonal antibody directed against programmed death-ligand 1 (PD-L1), in patients with HCC who have not received prior systemic therapy. The trial is being conducted as part of a clinical collaboration between AVEO and AstraZeneca.
"In a number of solid tumor indications, including metastatic liver cancer, VEGF-TKI/immunotherapy combinations are playing an increasingly important role in initial treatment selection," said Renuka Iyer, M.D., senior author of the publication and Professor of Oncology and Co-Director, Liver and Pancreas Tumor Center, Roswell Park Comprehensive Cancer Center. "Central to these combinations is the tolerability of the VEGF-TKI backbone. With an early efficacy signal and favorable tolerability profile demonstrated in this study, tivozanib shows great potential as a VEGF-TKI for such combinations. I look forward to seeing this potential elucidated in the ongoing DEDUCTIVE study of tivozanib and durvalumab in HCC."
About Tivozanib
Tivozanib (FOTIVDA) is an oral, once-daily, vascular endothelial growth factor receptor (VEGFR) 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 is being studied in the TIVO-3 trial, which is intended to support a regulatory submission of tivozanib in the U.S. as a treatment for relapsed/refractory RCC. 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.