Zhao Mingchuan, Hu Xichun, Zhuang Pengpeng, Zeng Aiping, Yu Yan, Chen Zhendong, Sun Hongmei, Yang Weihua, Sheng Lili, Peng Peijian, Wang Jingfen, Yi Tienan, Bi Minghong, Shi Huaqiu, Ni Mingli, Dai Xiumei, Hu Changlu, Xu Hongjie, Lv Dongqing, Li Qingshan, Lei Kaijian, Yuan Xia, Jiang Ou, Wang Xicheng, Hu Baihui, Hou Zhe, Su Zhaoping, Zheng Song, Zhou Ming, Dou Changlin
Fudan University Shanghai Cancer Center, PR China.
Shandong Boan Biotechnology Co., Ltd., PR China.
J Bone Oncol. 2025 Jan 28;51:100661. doi: 10.1016/j.jbo.2025.100661. eCollection 2025 Apr.
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.
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.
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.
This study demonstrated the equivalent efficacy and safety of LY01011 to denosumab in patients with BM.
地诺单抗（Xgeva®）是预防骨转移（BM）患者骨相关事件（SREs）的标准治疗药物。本试验旨在评估LY01011与地诺单抗在疗效和安全性方面的等效性。
符合条件的实体瘤骨转移患者按1:1比例随机分组，在为期12周的双盲治疗期内每四周皮下注射120mg LY01011或120mg地诺单抗，然后所有入组患者继续接受LY01011治疗直至第53周。主要终点是第13周时尿I型胶原N端交联肽水平相对于尿肌酐水平（uNTX/uCr）较基线变化的自然对数。其他终点包括uNTX/uCr比值、血清骨特异性碱性磷酸酶水平变化、抗药抗体和中和抗体状态、不良事件和SREs。
850例符合条件的患者被随机分为LY01011组（n = 424）或地诺单抗组（n = 426）。第13周时，LY01011组uNTX/uCr比值较基线变化的自然对数的最小二乘均值（SEs）为-1.810（0.0404），地诺单抗组为-1.791（0.0406）。两组间的最小二乘均值差异[90%CI]在等效区间（-0.135，0.135）内为-0.019[-0.110，0.073]，达到预定的主要终点。不良事件、抗药抗体和药代动力学数据无统计学显著差异。
本研究证明LY01011在骨转移患者中与地诺单抗疗效和安全性等效。
