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

Christos Fountzilas, Medhavi Gupta, Sunyoung Lee, Smitha Krishnamurthi, Bassam Estfan, Katy Wang, Kristopher Attwood, John Wilton, Robert Bies, Wiam Bshara, Renuka Iyer

Research output: Contribution to journalArticle

1 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)963-970
Number of pages8
JournalBritish Journal of Cancer
Volume122
Issue number7
DOIs
StatePublished - Mar 31 2020
Externally publishedYes

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Fountzilas, C., Gupta, M., Lee, S., Krishnamurthi, S., Estfan, B., Wang, K., Attwood, K., Wilton, J., Bies, R., Bshara, W., & Iyer, R. (2020). A multicentre phase 1b/2 study of tivozanib in patients with advanced inoperable hepatocellular carcinoma. British Journal of Cancer, 122(7), 963-970. https://doi.org/10.1038/s41416-020-0737-6