Single Center, Randomized, Double-blind, Parallel Controlled Phase I Clinical Trial Comparing the Pharmacokinetic and Safety Similarities of Recombinant Humanized Anti-Human Epidermal Growth Factor Receptor Monoclonal Antibody Injection (HS627)(2 Kinds Of Specification)with PERJETA after a Single Dose Intravenous in Dripping in Healthy

开始日期2022-03-27

申办/合作机构

青岛大学附属医院

CTR20180715 / Active, not recruiting临床1期

评价注射用重组抗HER2人源化单克隆抗体（WLB301）药代动力学、免疫原性及安全性的随机、双盲、原研药对照的临床研究

主要目的：评价单次给药后WLB301与注射用曲妥珠单抗（赫赛汀®）的主要药代动力学参数AUC(0-t)的相似性；次要目的： 1.评价单次给药后WLB301与注射用曲妥珠单抗（赫赛汀®）AUC0-∞及Cmax的相似性； 2.评价静脉给药后WLB301与赫赛汀®在男性志愿者中不良事件发生率的差异，给药后ADA、实验室、生命体征、心电图、超声心动图、体格检查结果的变化。

开始日期2018-12-10

申办/合作机构

深圳万乐药业有限公司

ChiCTR2000041577 / Completed临床1期IIT

Comparative pharmacokinetics of recombinant anti-HER2 humanized monoclonal antibody for injection in a single dose in healthy volunteers

开始日期2014-03-06

申办/合作机构-

100 项与重组抗HER2人源化单抗 (深圳万乐药业) 相关的临床结果

登录后查看更多信息

100 项与重组抗HER2人源化单抗 (深圳万乐药业) 相关的转化医学

登录后查看更多信息

100 项与重组抗HER2人源化单抗 (深圳万乐药业) 相关的专利（医药）

登录后查看更多信息

项与重组抗HER2人源化单抗 (深圳万乐药业) 相关的文献（医药）

2024-05-01·European Journal of Drug Metabolism and Pharmacokinetics

A Phase I Clinical Study Comparing the Pharmacokinetics, Safety, and Immunogenicity of GB221 Injection and Trastuzumab (Herceptin®) in Healthy Chinese Adults

Article

作者: Song, Haifeng ; Wang, Xuan ; Zhu, Yu ; Fang, Yi ; Li, Xianbo ; He, Jin ; Xiao, Shuangshuang ; Liang, Xintong ; Hu, Zhiqin ; Zhan, Yaoxuan ; Wang, Xiaole ; Wang, Tenghua ; Ou, Lun ; Tian, Jingyuan ; Liu, Haiyan ; Li, Chen ; Chen, Liming ; Zheng, Qingshan ; Li, Tong ; Li, Yongmei

BACKGROUND AND OBJECTIVEGB221 is a recombinant humanized anti-HER2 monoclonal antibody. The purpose of this study was to evaluate the pharmacokinetic, safety, and immunogenicity of GB221 in healthy Chinese adults in comparison to trastuzumab (Herceptin^®).METHODSIn this randomized, double-blind, parallel-group phase I clinical trial, 88 subjects were randomized 1:1 to receive a single intravenous infusion (90-100 min) of GB221 or trastuzumab (6 mg/kg). The primary pharmacokinetic parameters-maximum observed serum concentration (C_max), area under the serum concentration-time curve from zero to the last quantifiable concentration at time t (AUC_0-t), and area under the serum concentration-time curve from time zero to infinity (AUC_0-∞)-of GB221 and trastuzumab were compared to establish whether the 90% confidence interval (CI) attained the 80-125% bioequivalence standard. Safety and immunogenicity were also evaluated.RESULTSThe GB221 group (n = 43) and the trastuzumab group (n = 44) showed similar pharmacokinetic characteristics. The geometric mean ratios (90% CI) of C_max, AUC_0-t, and AUC_0-∞ between the two groups were 107.53% (102.25-113.07%), 108.31% (103.57-113.26%), and 108.34% (103.57-113.33%), respectively. The incidence of treatment-emergent adverse events (TEAEs) was 83.7% (36/43) of the subjects in the GB221 group and 95.5% (42/44) of the subjects in the trastuzumab group. No subjects withdrew from the trial due to TEAEs, and there were no occurrences of serious adverse events. All subjects tested negative for antidrug antibodies (ADA).CONCLUSIONGB221 demonstrated similar pharmacokinetics to trastuzumab and comparable safety and immunogenicity in healthy Chinese adults.

2023-06-30·Translational cancer research

Bioactivity of recombinant humanized monoclonal antibody against HER2 in-vivo and in-vitro and its mechanism of action in ovarian cancer.

Article

作者: Zeng, Jinfeng ; Guan, Rui ; Zhang, Hui

BackgroundHuman epidermal growth factor receptor 2 (HER2) protein is overexpressed on the surface of various epithelial ovarian cancer tissues, mediates the proliferation, differentiation, metastasis, and signal transduction of tumor cells, and thus is a potential cancer therapeutic target. However, its research in ovarian cancer is still limited, and how to quickly obtain a large number of antibodies remains a concern for researchers.MethodsIn this study, we expressed the recombinant anti-HER2 humanized monoclonal antibody (rhHER2-mAb) in human embryonic kidney 293 (HEK293) cells through transient gene expression (TGE) technology by constructing a mammalian cell expression vector. Firstly, the transfection conditions has been optimized, the ratio of light chain (LC) and heavy chain (HC) was optimized in the range of 4:1 to 1:2 and the ration DNA and polyethyleneimine was optimized in the range of 4:1 to 1:1. The antibody was purified by rProtein A affinity chromatography, and its mediated antibody-dependent cellular cytotoxicity (ADCC) was identified by lactate dehydrogenase release assays. The anti-tumor activity of rhHER2-mAb was evaluated in non-obese diabetic/severe combined immunodeficiency mice.ResultsThe expression of rhHER2-mAb in the HEK293F cells was at the highest level (100.5 mg/L) when the DNA/polyethyleneimine and light-chain/heavy-chain ratios were 1:4 and 1:2, respectively. The half-maximal inhibitory concentration of the ADCC of the antibodies against the SK-OV-3, OVCAR-3, and A-2780 cells were 12.36, 5.43, and 102.90 ng/mL, respectively. The animal experiments with the mice showed that rhHER2-mAb effectively inhibited the growth (P<0.01) of the SK-OV-3 tumors at a dose of 10 mg/kg.ConclusionsTGE technology allows us to quickly obtain a large number of anti-HER2 antibodies compared to the traditional method of constructing stable cell lines, and its in vitro and in vivo studied shows that our anti-HER2 antibody have higher affinity and better biological activity bioactivity (P<0.01) compared to Herceptin. Our findings provide novel insights into the development and production of future biotechnology-based drugs using the TGE technology of HEK293F.

2022-08-01·Investigational New Drugs

Rare ocular toxicity induced by pertuzumab/QL1209 in healthy chinese subjects: case reports and whole-exome sequencing analysis

Article

作者: Hu, Zhanqing ; Zou, Chan ; Ma, Junlong ; Yang, Guoping ; Guo, Chengxian ; Huang, Jie ; Chen, Wenjing

Pertuzumab is a recombinant anti-HER2 humanized monoclonal antibody widely used for the adjuvant treatment of HER2-positive breast cancer. Its safety is well established with the most common adverse effects being diarrhea and rash. To our knowledge, severe pertuzumab-induced ocular adverse events have never been reported. Herein, we describe several cases of pertuzumab/QL1209 (pertuzumab biosimilar)-induced blurred vision in healthy Chinese male subjects after a single injection of 420 mg pertuzumab/QL1209. Persistent optic nerve damage and vision loss occurred in the most severe case even after ophthalmic treatment. We conducted whole-exome sequencing (WES) of DNA samples from 5 cases and 13 controls to analyze the potential genetic factors and identified some associated variants (rs80303690 in RBM24, rs117375173 in CASR, rs1805097 in IRS2, and rs1227049 in CDH23). Furthermore, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways and Gene Ontology (GO) terms gene enrichment analyses were carried out for differentially expressed genes clustered in the PI3K/AKT/mTOR and Ras/Raf/MAPK signaling pathways, which were exactly activated by HER2 phosphorylation. In summary, this is the first report describing the occurrence of ocular toxicity induced by pertuzumab in the Chinese population and exploring the possible genetic mechanisms. These findings could provide evidence for clinicians to raise concerns about the risk of ocular toxicity with the clinical use of pertuzumab.

100 项与重组抗HER2人源化单抗 (深圳万乐药业) 相关的药物交易

登录后查看更多信息