TY - JOUR
T1 - A multicentre phase 1b/2 study of tivozanib in patients with advanced inoperable hepatocellular carcinoma
AU - Fountzilas, Christos
AU - Gupta, Medhavi
AU - Lee, Sunyoung
AU - Krishnamurthi, Smitha
AU - Estfan, Bassam
AU - Wang, Katy
AU - Attwood, Kristopher
AU - Wilton, John
AU - Bies, Robert
AU - Bshara, Wiam
AU - Iyer, Renuka
N1 - Publisher Copyright:
© 2020, The Author(s), under exclusive licence to Cancer Research UK.
PY - 2020/3/31
Y1 - 2020/3/31
N2 - 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.
AB - 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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U2 - 10.1038/s41416-020-0737-6
DO - 10.1038/s41416-020-0737-6
M3 - Article
C2 - 32037403
AN - SCOPUS:85079461189
SN - 0007-0920
VL - 122
SP - 963
EP - 970
JO - British journal of cancer
JF - British journal of cancer
IS - 7
ER -