HLX11，一种拟议的曲妥珠单抗生物类似药：与三种参考生物制品（美国、欧盟和中国批准的曲妥珠单抗）相比，在健康男性受试者中的药代动力学、免疫原性和安全性特征。
HLX11, a Proposed Pertuzumab Biosimilar: Pharmacokinetics, Immunogenicity, and Safety Profiles Compared to Three Reference Biologic Products (US-, EU-, and CN-Approved Pertuzumab) Administered to Healthy Male Subjects.
机构信息
Department of Clinical Pharmacology, The Second Hospital of Anhui Medical University, Hefei, Anhui, People's Republic of China.
Anhui Provincial Institute of Translational Medicine, Hefei, Anhui, People's Republic of China.
出版信息
BioDrugs. 2022 May;36(3):393-409. doi: 10.1007/s40259-022-00534-w. Epub 2022 May 20.
BACKGROUND
Pertuzumab is a humanized monoclonal antibody for the treatment of breast cancer. HLX11 is a biosimilar of pertuzumab developed by Shanghai Henlius Biotech, Inc. We conducted a bioequivalence study for HLX11 and pertuzumab (United States [US]-, European Union [EU]-, and China [CN]-approved products).
OBJECTIVES
This study compared the biosimilarity in pharmacokinetics (PK), safety, and immunogenicity between HLX11 and reference pertuzumab (approved in the US, the EU, and CN) in healthy Chinese male participants after a single infusion and further characterized the PK profile of HLX11.
METHODS
Eligible individuals were randomized 1:1:1:1 to receive a single dose of 420 mg HLX11, US-, EU-, or CN-pertuzumab via intravenous infusion over 60 min. The primary endpoints were maximum serum drug concentration (C), area under the serum concentration-time curve (AUC) from time 0 to time of the last quantifiable concentration (AUC), and AUC from time 0 to infinity (AUC). PK bioequivalence was established if the 90% confidence intervals (CIs) of the geometric mean ratios of the primary endpoints were between 80.0 and 125.0%. Secondary endpoints included other PK parameters, safety, and immunogenicity.
RESULTS
A total of 160 participants were enrolled and randomly assigned to each group (n = 40 per group). The 90% CIs of the geometric mean ratios of the primary endpoints were all within the prespecified equivalence margins (HLX11 vs. pertuzumab [US-, EU-, CN-approved products]: C 97.03-115.06%, 91.39-109.80%, 94.53-110.65%; AUC 87.65-99.68%, 87.07-100.79%, 86.29-101.09%; AUC 87.66-99.90%, 87.54-101.05%, 89.23-103.20%). The incidence of adverse drug reactions was comparable across the four groups. The presence of anti-drug antibodies or neutralizing antibodies had no obvious effect on PK.
CONCLUSION
The PK, safety, and immunogenicity of HLX11 were highly similar to those of reference pertuzumab (US-, EU-, CN-approved products). The established bioequivalence supports further clinical trials of HLX11 in cancer treatment.
TRIAL REGISTRATION
This study was registered with ClinicalTrials.gov (NCT04411550) and Chinadrugtrials.org.cn (CTR20200618).
背景
曲妥珠单抗是一种用于治疗乳腺癌的人源化单克隆抗体。HLX11 是上海复宏汉霖生物制药有限公司开发的曲妥珠单抗生物类似药。我们进行了一项 HLX11 与曲妥珠单抗（美国、欧盟和中国批准的产品）的生物等效性研究。
目的
本研究比较了单次输注后 HLX11 与参考曲妥珠单抗（美国、欧盟和中国批准）在健康中国男性参与者中的药代动力学（PK）、安全性和免疫原性的相似性，并进一步描述了 HLX11 的 PK 特征。
方法
符合条件的个体按 1:1:1:1 的比例随机分配，接受 420mg HLX11、美国、欧盟或中国批准的曲妥珠单抗静脉输注 60 分钟。主要终点为最大血清药物浓度（C）、从 0 到最后可定量浓度的时间（AUC）的血清浓度-时间曲线下面积（AUC）和从 0 到无穷大的 AUC（AUC）。如果主要终点的几何均数比值的 90%置信区间（CI）在 80.0 到 125.0%之间，则认为 PK 等效。次要终点包括其他 PK 参数、安全性和免疫原性。
结果
共纳入 160 名参与者，按 1:1:1:1 的比例随机分配至每组（每组 40 名）。主要终点的几何均数比值的 90%CI 均在预设的等效区间内（HLX11 与曲妥珠单抗[美国、欧盟、中国批准的产品]：C 97.03-115.06%、91.39-109.80%、94.53-110.65%；AUC 87.65-99.68%、87.07-100.79%、86.29-101.09%；AUC 87.66-99.90%、87.54-101.05%、89.23-103.20%）。四组中不良反应的发生率相当。抗药物抗体或中和抗体的存在对 PK 没有明显影响。
结论
HLX11 的 PK、安全性和免疫原性与参考曲妥珠单抗（美国、欧盟和中国批准的产品）高度相似。已建立的生物等效性支持 HLX11 在癌症治疗中的进一步临床试验。
试验注册
本研究在 ClinicalTrials.gov（NCT04411550）和 Chinadrugtrials.org.cn（CTR20200618）上注册。
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