Yan Song; Jinwan Wang; Xiubao Ren; Jie Jin; Li Mao; Chris Liang; Lieming Ding; Lin Yang

doi:10.21147/j.issn.1000-9604.2021.01.11

Chin J Cancer Res> 2021, Vol. 33> Issue(1) : 103-114

Citation: Song Y, Wang J, Ren X, Jin J, Mao L, Liang C, Ding L, Yang L. Vorolanib, an oral VEGFR/PDGFR dual tyrosine kinase inhibitor for treatment of patients with advanced solid tumors: An open-label, phase I dose escalation and dose expansion trial. Chin J Cancer Res 2021;33(1):103-114. doi: 10.21147/j.issn.1000-9604.2021.01.11 shu

Vorolanib, an oral VEGFR/PDGFR dual tyrosine kinase inhibitor for treatment of patients with advanced solid tumors: An open-label, phase I dose escalation and dose expansion trial

1.
Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
2.
Department of Biotherapy, Tianjin Medical University Cancer Institute and Hospital, Tianjin 300060, China
3.
Department of Urology, Peking University First Hospital, Beijing 100034, China
4.
Betta Pharmaceuticals Co., Ltd., Hangzhou 311100, China

Correspondence to: Lin Yang. Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China. Email: linyang@cicams.ac.cn
Submitted: Sep 29, 2020
Accepted for publication: Dec 29, 2020

Figures(4) / Tables(5)

Objective: This study evaluated the safety and preliminary efficacy of vorolanib, a novel tyrosine kinase inhibitor, for treatment of patients with advanced solid tumors. Methods: During dose escalation, patients received increasing doses of oral vorolanib (50−250 mg once daily) in cycles of four weeks for up to one year. During dose expansion, patients received recommended doses (100 and 200 mg) in 4-week cycles. The primary endpoint was to determine the safety and maximum tolerated dose and/or the recommended phase II dose (RP2D). The severity and type of adverse drug reactions (ADRs) were assessed using the Common Terminology Criteria for Adverse Events version 4.0. The second endpoint was preliminary efficacy in terms of objective response and progression-free survival (PFS). Results: No dose-limiting toxicity occurred during dose escalation (50−250 mg). Five (26.3%) patients in the escalation cohort (n=19) and 12 (48.0%) in the expansion cohort (n=25) experienced grade 3 ADRs. The most common ADRs were hair color changes, fatigue, portal hypertension, hypertriglyceridemia, and proteinuria. During dose expansion, the patients treated with 200 mg and 100 mg (once daily) showed an objective response rate of 22.2% and 5.9%, respectively; the disease control rate was 88.9% and 73.3%, respectively; the median PFS was 9.9 [95% confidence interval (95% CI): 7.4−not reached] months and 3.8 (95% CI: 1.9−not reached) months, respectively. Conclusions: Oral vorolanib at a dose of 200 mg (once daily) exhibited an acceptable safety profile and favorable clinical benefit for patients with advanced solid tumors. The RP2D for vorolanib was determined to be 200 mg as a daily regimen.
- Vorolanib;
- TKI;
- VEGFR;
- PDGFR;
- advanced solid tumor
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