■denosumab生物仿制药的生物等效性尚未在53周内进行研究,多中心,大规模,正面交锋的审判.临床上有效的生物仿制药可能有助于增加实体瘤相关骨转移患者对denosumab的使用。
■基于大规模的头对头研究,建立MW032与denosumab在实体瘤相关骨转移患者中的生物相似性。
■在这53周,随机化,双盲,第三阶段等效试验,我们从中国46个临床地点招募了有骨转移的实体瘤患者.总的来说,对856名患者进行了筛选,708名符合条件的患者被随机分配接受MW032或denosumab。
■患者被随机分配(1:1),每4周皮下接受MW032或参考denosumab,直到第49周。
■主要终点是从基线到第13周自然对数转换的尿N-端肽/肌酐比值(uNTx/uCr)的百分比变化。
■在701个可评估的患者中(MW032组350个,denosumab组351个),平均(范围)年龄为56.1(22.0~86.0)岁,460例患者为女性(65.6%).从基线到第13周,MW032组uNTx/uCr的平均变化为-72.0%(95%CI,-73.5%至-70.4%),denosumab组为-72.7%(95%CI,-74.2%至-71.2%)。这些百分比变化对应于-1.27和-1.30的平均对数比,或0.02的差异。差异的90%CI(-0.04至0.09)在等效界限(-0.13至0.13)内;在53周内,每个时间点的uNTx/uCr和骨特异性碱性磷酸酶(s-BALP)的平均变化也相似。uNTx/uCr变化差异为0.015(95%CI,-0.06~0.09),-0.02(95%CI,-0.09至0.06),在第5、25、37和53周分别为-0.05(95%CI,-0.13至0.03)和0.001(95%CI,-0.10至0.10)。s-BALP变化差异为-0.006(95%CI,0.06~0.05),0.00(95%CI,-0.07至0.07),-0.085(95%CI,-0.18至0.01),-0.09(95%CI,-0.20至0.02),分别在第5、13、25、37和53周和-0.13(95%CI,-0.27至0.004)。在骨骼相关事件的发生率(-1.4%;95%CI,-5.8%至3.0%)或首次研究骨骼相关事件的时间(未调整的HR,0.86;P=.53;多重性调整后的HR,0.87;P=.55)在2组中。
■MW032和denosumab在疗效上是生物相似的,群体药代动力学,和安全概况。denosumab生物仿制药的可用性可能会扩大denosumab的使用范围,并减轻晚期肿瘤患者的药物负担。
■ClinicalTrials.gov标识符:NCT04812509。
UNASSIGNED: The bioequivalence of denosumab biosimilar has yet to be studied in a 53-week, multicenter, large-scale, and head-to-head trial. A clinically effective biosimilar may help increase access to denosumab in patients with solid tumor-related bone metastases.
UNASSIGNED: To establish the biosimilarity of MW032 to denosumab in patients with solid tumor-related bone metastases based on a large-scale head-to-head study.
UNASSIGNED: In this 53-week, randomized, double-blind, phase 3 equivalence trial, patients with solid tumors with bone metastasis were recruited from 46 clinical sites in
China. Overall, 856 patients were screened and 708 eligible patients were randomly allocated to receive either MW032 or denosumab.
UNASSIGNED: Patients were randomly assigned (1:1) to receive MW032 or reference denosumab subcutaneously every 4 weeks until week 49.
UNASSIGNED: The primary end point was percentage change from baseline to week 13 of natural logarithmic transformed urinary N-telopeptide/creatinine ratio (uNTx/uCr).
UNASSIGNED: Among the 701 evaluable patients (350 in the MW032 group and 351 in the denosumab group), the mean (range) age was 56.1 (22.0-86.0) years and 460 patients were women (65.6%). The mean change of uNTx/uCr from baseline to week 13 was -72.0% (95% CI, -73.5% to -70.4%) in the MW032 group and -72.7% (95% CI, -74.2% to -71.2%) in the denosumab group. These percent changes corresponded to mean logarithmic ratios of -1.27 and -1.30, or a difference of 0.02. The 90% CI for the difference (-0.04 to 0.09) was within the equivalence margin (-0.13 to 0.13); the mean changes of uNTx/uCr and bone-specific alkaline phosphatase (s-BALP) at each time point were also similar during 53 weeks. The differences of uNTx/uCr change were 0.015 (95% CI, -0.06 to 0.09), -0.02 (95% CI, -0.09 to 0.06), -0.05 (95% CI, -0.13 to 0.03) and 0.001 (95% CI, -0.10 to 0.10) at weeks 5, 25, 37, and 53, respectively. The differences of s-BALP change were -0.006 (95% CI, 0.06 to 0.05), 0.00 (95% CI, -0.07 to 0.07), -0.085 (95% CI, -0.18 to 0.01), -0.09 (95% CI, -0.20 to 0.02), and -0.13 (95% CI, -0.27 to 0.004) at weeks 5, 13, 25, 37 and 53, respectively. No significant differences were observed in the incidence of skeletal-related events (-1.4%; 95% CI, -5.8% to 3.0%) or time to first on-study skeletal-related events (unadjusted HR, 0.86; P = .53; multiplicity adjusted HR, 0.87; P = .55) in the 2 groups.
UNASSIGNED: MW032 and denosumab were biosimilar in efficacy, population pharmacokinetics, and safety profile. Availability of denosumab biosimilars may broaden the access to denosumab and reduce the drug burden for patients with advanced tumors.
UNASSIGNED: ClinicalTrials.gov Identifier: NCT04812509.