Efficacy and Safety of Denosumab Biosimilar QL1206 Versus Denosumab in Patients with Bone Metastases from Solid Tumors: A Randomized Phase III Trial

作者：Huiping Li, Yan Huang, Zhendong Chen, Aiping Zeng, Helong Zhang, Yan Yu, Shihong Wei, Qingshan Li, Xiaojia Wang, Xiangcai Wang, Xiuwen Wang, Runxiang Yang, Xiumei Dai, Minghong Bi, Tao Sun, Qingyuan Zhang, Cuicui Han, Yu-Jie Li, Xiaoyan Kang, Yaxin Liu, Li Zhang · 发表于：BioDrugs · 年份：2023 · DOI：10.1007/s40259-023-00579-5 · 被引用次数：11 · 研究领域：Biosimilars and Bioanalytical Methods、Bone health and treatments、Prostate Cancer Treatment and Research

BACKGROUND: Denosumab has been approved for the treatment of bone metastases from solid tumors. QL1206 is the first denosumab biosimilar and needs to be compared with denosumab in a phase III trial. OBJECTIVE: This phase III trial aims to compare the efficacy, safety, and pharmacokinetics between QL1206 and denosumab in patients with bone metastases from solid tumors. METHODS: This randomized, double-blind, phase III trial was conducted in 51 centers in China. Patients aged 18-80 years, with solid tumors and bone metastases, and an Eastern Cooperative Oncology Group performance status of 0-2 were eligible. This study was divided into a 13-week double-blind period, a 40-week open-label period, and a 20-week safety follow-up period. In the double-blind period, patients were randomly assigned (1:1) to receive three doses of QL1206 or denosumab (120 mg subcutaneously every 4 weeks, each). Randomization was stratified by tumor types, previous skeletal-related events, and current systemic anti-tumor therapy. In the open-label period, up to ten doses of QL1206 could be given in both groups. The primary endpoint was percentage change in urinary N-telopeptide/creatinine ratio (uNTX/uCr) from baseline to Week 13. Equivalence margins were ± 0.135. Secondary endpoints included percentage change in uNTX/uCr at Week 25 and 53, percentage change in serum bone-specific alkaline phosphatase at Week 13, 25, and 53, and time to on-study skeletal-related events. The safety profile was evaluated ...