Sulfatinib, a novel kinase inhibitor, in patients with advanced solid tumors: results from a phase I study
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Jian Ming Xu1, Yan Wang1, Yu Ling Chen1, Ru Jia1, Jie Li2, Ji Fang Gong2, Jing Li3, Chuan Qi3, Ye Hua3, Cui Rong Tan3, Jian Wang4, Ke Li4, Yang Sai4, Feng Zhou5, Yong Xin Ren5, Wei Guo Qing5, Hong Jia6, Wei Guo Su6 and Lin Shen2
1Department of Gastrointestinal Oncology, The Affiliated Hospital Cancer Center (The 307th Hospital of Chinese People’s Liberation Army), Academy of Military Medical Sciences, Beijing, China
2Department of Gastrointestinal Oncology, Peking University Cancer Hospital, Beijing, China
3Clinical and Regulatory Department, Hutchison MediPharma Limited, Shanghai, China
4Drug Metabolism and Pharmacokinetic Department, Hutchison MediPharma Limited, Shanghai, China
5Oncology Department, Hutchison MediPharma Limited, Shanghai, China
6Chemistry Department, Hutchison MediPharma Limited, Shanghai, China
Jian Ming Xu, email: [email protected]
Lin Shen, email: [email protected]
Keywords: phase I clinical trial, neuroendocrine tumor, solid tumor, sulfatinib, tyrosine kinase inhibitor
Received: October 28, 2016 Accepted: December 05, 2016 Published: February 01, 2017
Sulfatinib is a small molecule kinase inhibitor that targets tumor angiogenesis and immune modulation. This phase I study (NCT02133157) investigated the safety, pharmacokinetic characteristics, and preliminary anti-tumor activity of sulfatinib in patients with advanced solid tumors. The study included a dose-escalation phase (50-350 mg/day, 28-day cycle) with a Fibonacci (3+3) design, and a tumor-specific expansion phase investigating the tumor response to treatment. Two sulfatinib formulations were assessed: formulation 1 (5, 25, and 50 mg capsules) and formulation 2 (50 and 200 mg capsules). Seventy-seven Chinese patients received oral sulfatinib; the maximum tolerated dose was not reached. Dose-limiting toxicities included abnormal hepatic function and coagulation tests, and upper gastrointestinal hemorrhage. The most common treatment-related adverse events were proteinuria, hypertension and diarrhea. Among 34 patients receiving sulfatinib formulation 2, one patient with hepatocellular carcinoma and eight with neuroendocrine tumors exhibited a partial response; 15 had stable disease. The objective response rate was 26.5% (9/34) and the disease control rate was 70.6% (24/34). Pharmacokinetic, safety, and efficacy data supported continuous oral administration of sulfatinib at 300 mg as the recommended phase II dose. Sulfatinib exhibited an acceptable safety profile and encouraging antitumor activity in patients with advanced solid tumors, particularly neuroendocrine tumors.
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