Schwabe Christian, Wynne Chris, Dyapa Dayaker Reddy, Prajapati Arpitkumar, Dadke Disha
New Zealand Clinical Research, Auckland, New Zealand.
CuraTeQ Biologics Private Limited, Unit XVII, Sy. No. 77 & 78, Indrakaran (v), Sangareddy Dist, Hyderabad, 502329, India.
Oncol Ther. 2024 Sep;12(3):477-490. doi: 10.1007/s40487-024-00289-0. Epub 2024 Jul 7.
This study evaluated the pharmacokinetic (PK) equivalence between BP02 (a proposed trastuzumab biosimilar) and the reference trastuzumab approved in the EU (EU-trastuzumab) and the US (US-trastuzumab).
In this phase 1, double-blind, parallel-group trial, 111 healthy male volunteers were randomized 1:1:1 to receive a single 6-mg/kg intravenous infusion of BP02, EU-trastuzumab, or US-trastuzumab and were evaluated for 78 days. Serum drug concentration-time data were analyzed by non-compartmental methods. The PK similarity of BP02 to the two reference products, and between EU-trastuzumab and US-trastuzumab, was determined using the standard 80-125% bioequivalence criteria.
Baseline demographics for the 111 subjects with evaluable pharmacokinetics were similar across all treatment groups. PK profiles were similar for the three products. The 90% confidence intervals (CIs) for the ratios of area under the serum concentration-time curve (AUC) from the time of dosing to infinity (AUC), AUC from the time of dosing until the time of the last quantifiable concentration (AUC), and peak serum concentration of trastuzumab (C) were within 80% to 125% for all three pairwise comparisons. Adverse events (AEs) were similar across all arms, with treatment-related AEs reported by 73.0%, 73.0%, and 89.2% of the subjects in the BP02, EU-trastuzumab, and US-trastuzumab groups, respectively. The most common AEs were headache, infusion-related reactions, and upper-respiratory-tract infections. Four subjects-three in the US-trastuzumab group and one in the BP02 group-discontinued the study due to AEs. All post-dose samples except for two tested negative for anti-drug antibodies.
This study demonstrates the PK similarity among BP02, EU-trastuzumab, and US-trastuzumab. The safety and immunogenicity profiles observed for the three products in this study are consistent with previous reports for trastuzumab.
ANZCTR number: ACTRN12621000573853.
本研究评估了BP02（一种拟用的曲妥珠单抗生物类似药）与在欧盟（欧盟曲妥珠单抗）和美国（美国曲妥珠单抗）获批的参比曲妥珠单抗之间的药代动力学（PK）等效性。
在这项1期双盲平行组试验中，111名健康男性志愿者按1:1:1随机分组，接受单次6 mg/kg静脉输注BP02、欧盟曲妥珠单抗或美国曲妥珠单抗，并进行78天的评估。采用非房室方法分析血清药物浓度-时间数据。使用标准的80%-125%生物等效性标准确定BP02与两种参比产品之间以及欧盟曲妥珠单抗和美国曲妥珠单抗之间的PK相似性。
111名具有可评估药代动力学的受试者的基线人口统计学特征在所有治疗组中相似。三种产品的PK曲线相似。给药至无穷大时血清浓度-时间曲线下面积（AUC）的比值、给药至最后可定量浓度时的AUC以及曲妥珠单抗的血清峰浓度（C）的90%置信区间（CI）在所有三个两两比较中均在80%至125%之间。所有组的不良事件（AE）相似，BP02组、欧盟曲妥珠单抗组和美国曲妥珠单抗组分别有73.0%、73.0%和89.2%的受试者报告了与治疗相关的AE。最常见的AE是头痛、输液相关反应和上呼吸道感染。四名受试者——美国曲妥珠单抗组三名，BP02组一名——因AE退出研究。除两份样本外，所有给药后样本的抗药抗体检测均为阴性。
本研究证明了BP02、欧盟曲妥珠单抗和美国曲妥珠单抗之间PK相似。本研究中观察到的三种产品的安全性和免疫原性特征与先前曲妥珠单抗的报告一致。
澳大利亚和新西兰临床试验注册中心编号：ACTRN12621000573853。
