A multicenter, randomized, double-blind trial comparing LY01011, a biosimilar, with denosumab (Xgeva®) in patients with bone metastasis from solid tumors

IF 3.4 2区医学 Q2 Medicine

Journal of Bone Oncology Pub Date : 2025-01-28 DOI:10.1016/j.jbo.2025.100661

Mingchuan Zhao , Xichun Hu , Pengpeng Zhuang , Aiping Zeng , Yan Yu , Zhendong Chen , Hongmei Sun , Weihua Yang , Lili Sheng , Peijian Peng , Jingfen Wang , Tienan Yi , Minghong Bi , Huaqiu Shi , Mingli Ni , Xiumei Dai , Changlu Hu , Hongjie Xu , Dongqing Lv , Qingshan Li , Changlin Dou

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引用次数: 0

Abstract

Introduction

Denosumab (Xgeva®) is a standard treatment for the prevention of skeletal-related events (SREs) in patients with bone metastases (BM). This trial was designed to assess the equivalence of LY01011 to denosumab in terms of efficacy and safety.

Materials and methods

Eligible patients with BM from solid tumors were randomized at a 1:1 ratio to receive 120 mg of LY01011 or 120 mg of denosumab subcutaneously every four weeks during a 12-week double-blind treatment period, and then all enrolled patients continued to receive LY01011 until week 53. The primary endpoint was the natural logarithm of change of the urinary N-terminal crosslinked telopeptide of type I collagen level normalized to the urine creatinine level (uNTX/uCr) at week 13 from baseline. Other endpoints included the uNTX/uCr ratio, serum bone-specific alkaline phosphatase level alteration, status of anti-drug antibodies and neutralizing antibodies, adverse events and SREs.

Results

850 eligible patients were randomized into the LY01011 group (n = 424) or the denosumab group (n = 426). The least-squares means (SEs) of the natural logarithms of the changes in the uNTX/uCr ratios at week 13 from baseline were −1.810 (0.0404) in the LY01011 group and −1.791 (0.0406) in the denosumab group. The LSM difference [90 % CI] between two arms was −0.019 [-0.110, 0.073] within the equivalence margins (−0.135, 0.135) and met the predetermined primary endpoint. The AEs, ADAs and the PK data showed no statistically significant difference.

Conclusions

This study demonstrated the equivalent efficacy and safety of LY01011 to denosumab in patients with BM.

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来源期刊

Journal of Bone Oncology ONCOLOGY-

CiteScore

7.20

自引率

2.90%

发文量

审稿时长

34 days

期刊介绍： The Journal of Bone Oncology is a peer-reviewed international journal aimed at presenting basic, translational and clinical high-quality research related to bone and cancer. As the first journal dedicated to cancer induced bone diseases, JBO welcomes original research articles, review articles, editorials and opinion pieces. Case reports will only be considered in exceptional circumstances and only when accompanied by a comprehensive review of the subject. The areas covered by the journal include: Bone metastases (pathophysiology, epidemiology, diagnostics, clinical features, prevention, treatment) Preclinical models of metastasis Bone microenvironment in cancer (stem cell, bone cell and cancer interactions) Bone targeted therapy (pharmacology, therapeutic targets, drug development, clinical trials, side-effects, outcome research, health economics) Cancer treatment induced bone loss (epidemiology, pathophysiology, prevention and management) Bone imaging (clinical and animal, skeletal interventional radiology) Bone biomarkers (clinical and translational applications) Radiotherapy and radio-isotopes Skeletal complications Bone pain (mechanisms and management) Orthopaedic cancer surgery Primary bone tumours Clinical guidelines Multidisciplinary care Keywords: bisphosphonate, bone, breast cancer, cancer, CTIBL, denosumab, metastasis, myeloma, osteoblast, osteoclast, osteooncology, osteo-oncology, prostate cancer, skeleton, tumour.