Reference Detail

Ref Type

Journal Article

PMID

(30642372)

Authors

Sun Y, Yang L, Hao X, Liu Y, Zhang J, Ning Z, Shi Y

Title

Phase I dose-escalation study of chiauranib, a novel angiogenic, mitotic, and chronic inflammation inhibitor, in patients with advanced solid tumors.

Journal	Vol	Issue	Date	Pages	Journal Short Title
Journal of hematology & oncology	12	1	2019 01 14	9	J Hematol Oncol

URL

Abstract Text

Chiauranib is a novel orally active multi-target inhibitor that simultaneously inhibits the angiogenesis-related kinases (VEGFR2, VEGFR1, VEGFR3, PDGFRα, and c-Kit), mitosis-related kinase Aurora B, and chronic inflammation-related kinase CSF-1R. This phase I dose-escalation study was to determine the maximum tolerated dose (MTD), safety, pharmacokinetics, and preliminary antitumor activity of chiauranib in patients with refractory advanced solid tumor and lymphoma.Eighteen patients were treated with continuous dosing of chiauranib from 10 to 65 mg once daily in a dose-escalation 3 + 3 design and evaluated in 28-day cycles. Pharmacokinetic profile of plasma chiauranib was analyzed in both single and multiple dose studies.Dose-limiting toxicity (DLT) as of grade 3 hypertension occurred in two patients at 65 mg/day, and one dose level below as MTD was 50 mg/day. The most common treatment-related adverse events included fatigue (61.1%), proteinuria (44.4%), hematuria (38.9%), hypothyroidism (38.9%), hypertriglyceridemia (33.3%), and hypertension (33.3%). A linear and dose-dependent pharmacokinetic profile of chiauranib was characterized with rapid absorption and slow elimination feature in both single and multiple dose studies. The accumulative exposure of chiauranib reached the steady state within 8 days and was approximately increased by twofold as those in the single dose study. No complete or partial response was observed, and 12 patients (66.7%) achieved stable disease (SD).Chiauranib demonstrated an acceptable safety and favorable pharmacokinetic profile with potential antitumor activity. Several phase Ib/II clinical studies are currently under further investigation.NCT, NCT02122809 . Registered 25 April 2014.

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Molecular Profile	Treatment Approach

Gene Name	Source	Synonyms	Protein Domains	Gene Description	Gene Role

Therapy Name	Drugs	Efficacy Evidence	Clinical Trials
Chiauranib	Chiauranib	0	2

Drug Name	Trade Name	Synonyms	Drug Classes	Drug Description
Chiauranib		CS2164	Aurkb Inhibitors 21 CSF1R Inhibitor 28 KIT Inhibitor 57 PDGFR-alpha Inhibitor 9 VEGFR Inhibitor (Pan) 36	Chiauranib (CS2164) is a multi-kinase inhibitor that inhibits AURKB, CSF-1R, VEGFRs, KIT, and PDGFRA, resulting in decreased tumor growth and angiogenesis (PMID: 28004478, PMID: 30642372).

Gene	Variant	Impact	Protein Effect	Variant Description	Associated with drug Resistance

Molecular Profile	Indication/Tumor Type	Response Type	Therapy Name	Approval Status	Evidence Type	Efficacy Evidence	References