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Clinical Trial
. 2020 Mar;122(7):963-970.
doi: 10.1038/s41416-020-0737-6. Epub 2020 Feb 10.

A multicentre phase 1b/2 study of tivozanib in patients with advanced inoperable hepatocellular carcinoma

Christos Fountzilas #  1 , Medhavi Gupta #  2 , Sunyoung Lee  3 , Smitha Krishnamurthi  4 , Bassam Estfan  4 , Katy Wang  2 , Kristopher Attwood  2 , John Wilton  2 , Robert Bies  5 , Wiam Bshara  2 , Renuka Iyer  2
Affiliations
Clinical Trial

A multicentre phase 1b/2 study of tivozanib in patients with advanced inoperable hepatocellular carcinoma

Christos Fountzilas et al. Br J Cancer. 2020 Mar.

Abstract

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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Conflict of interest statement

C.F.: AstraZeneca (consultation, fees paid to institute, outside the scope of submitted work).

Figures

Fig. 1
Fig. 1. Progression-free and overall survival in efficacy population.
Progression-free (a) and overall survival (b) in efficacy population.
Fig. 2
Fig. 2
RECIST response, waterfall plot.
Fig. 3
Fig. 3
Pre-dose sVEGFR-2, cycle 1 days 1 and 15.
See this image and copyright information in PMC

Comment in

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