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Updated: Dec 29, 2025

Transarterial Administration of Oncolytic Viruses for Locoregional Therapy of Orthotopic HCC in Rats
Published on: April 15, 2016
A multicentre phase 1b/2 study of tivozanib in patients with advanced inoperable hepatocellular carcinoma
Christos Fountzilas1, Medhavi Gupta2, Sunyoung Lee3
1Roswell Park Comprehensive Cancer Center, Buffalo, NY, USA. Christos.Fountzilas@RoswellPark.org.
Background:
Hepatocellular carcinoma (HCC) is a major cause of cancer-related death. It is a highly vascular tumour with multiple angiogenic factors, most importantly vascular endothelial growth factor (VEGF), involved in HCC progression. Tivozanib is an oral inhibitor of VEGFR-1/2/3 with promising activity against HCC in vivo.
Methods:
We conducted a phase 1b/2 study of tivozanib in patients with advanced HCC. The safety, dosing, pharmacokinetics, pharmacodynamics, and preliminary antineoplastic efficacy of tivozanib were evaluated.
Results:
Twenty-seven patients received at least one dose of tivozanib. Using a 3+3 design, the recommended phase 2 dose (RP2D) of tivozanib was determined to be 1 mg per os once daily, 21 days on-7 days off. The median progression-free and overall survival were 24 weeks and 9 months, respectively, for patients treated at RP2D. The overall response rate was 21%. Treatment was well tolerated. A significant decrease in soluble plasma VEGFR-2 was noted, assuring adequate target engagement.
Conclusions:
Although this study did not proceed to stage 2, there was an early efficacy signal with a very favourable toxicity profile. A phase 1/2 trial of tivozanib in combination with durvalumab is currently underway.
Trial Registration:
ClinicalTrials.gov NCT01835223, registered on 15 April 2013.
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