Yan Song1, Jinwan Wang1, Xiubao Ren2, Jie Jin3, Li Mao4, Chris Liang4, Lieming Ding4, Lin Yang1. 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.
Abstract
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.
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.
Authors: Robert J Motzer; Thomas E Hutson; Piotr Tomczak; M Dror Michaelson; Ronald M Bukowski; Olivier Rixe; Stéphane Oudard; Sylvie Negrier; Cezary Szczylik; Sindy T Kim; Isan Chen; Paul W Bycott; Charles M Baum; Robert A Figlin Journal: N Engl J Med Date: 2007-01-11 Impact factor: 91.245
Authors: Timothy L Jackson; David Boyer; David M Brown; Nauman Chaudhry; Michael Elman; Chris Liang; Denis O'Shaughnessy; Edward C Parsons; Sunil Patel; Jason S Slakter; Philip J Rosenfeld Journal: JAMA Ophthalmol Date: 2017-07-01 Impact factor: 7.389
Authors: Herbert I Hurwitz; Afshin Dowlati; Shermini Saini; Shawna Savage; A Benjamin Suttle; Diana M Gibson; Jeffrey P Hodge; Elmar M Merkle; Lini Pandite Journal: Clin Cancer Res Date: 2009-06-09 Impact factor: 12.531
Authors: Mohamed Hagras; Marwa A Saleh; Rogy R Ezz Eldin; Abdelrahman A Abuelkhir; Emad Gamil Khidr; Ahmed A El-Husseiny; Hesham A El-Mahdy; Eslam B Elkaeed; Ibrahim H Eissa Journal: J Enzyme Inhib Med Chem Date: 2022-12 Impact factor: 5.051
Authors: Nusayba A Bagegni; Haeseong Park; Katlyn Kraft; Maura O-Toole; Feng Gao; Saiama N Waqar; Lee Ratner; Daniel Morgensztern; Siddhartha Devarakonda; Manik Amin; Maria Q Baggstrom; Chris Liang; Giovanni Selvaggi; Andrea Wang-Gillam Journal: Cancer Chemother Pharmacol Date: 2022-03-05 Impact factor: 3.333