A Phase 1 randomized study compare the pharmacokinetics, safety and immunogenicity of HLX02 to reference CN- and EU-sourced trastuzumab in healthy subjects

Zhu, Xiaodong; Ding, Yanhua; Yu, Yang; Wang, M; Zhou, Wenjia; Wang, J; Zhang, H; Chai, Katherine; Zhang, X; Luk, Alvin; Jiang, Weidong; Liu, S; Zhang, Q

doi:10.1007/s00280-020-04196-9

Cited by 15 publications

(14 citation statements)

References 18 publications

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“…Hence, biosimilar drugs ameliorate this issue as they are nearly indistinguishable from the original drug and are less expensive. Recently, a biosimilar to trastuzumab, HLX02 [75], was shown to have near-identical clinical results when compared to trastuzumab [76]. Xu et al [59] reported that HXL02 showed similar efficacy and adverse effects in patients with HER2-positive recurrent or metastatic breast cancer compared to patients receiving trastuzumab (Table 1).…”

Section: Hlx02mentioning

confidence: 99%

Targeting mTOR and Glycolysis in HER2-Positive Breast Cancer

Holloway

Marignani

2021

Cancers

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Up to one third of all breast cancers are classified as the aggressive HER2-positive subtype, which is associated with a higher risk of recurrence compared to HER2-negative breast cancers. The HER2 hyperactivity associated with this subtype drives tumor growth by up-regulation of mechanistic target of rapamycin (mTOR) pathway activity and a metabolic shift to glycolysis. Although inhibitors targeting the HER2 receptor have been successful in treating HER2-positive breast cancer, anti-HER2 therapy is associated with a high risk of recurrence and drug resistance due to stimulation of the PI3K-Akt-mTOR signaling pathway and glycolysis. Combination therapies against HER2 with inhibition of mTOR improve clinical outcomes compared to HER2 inhibition alone. Here, we review the role of the HER2 receptor, mTOR pathway, and glycolysis in HER2-positive breast cancer, along with signaling mechanisms and the efficacy of treatment strategies of HER2-positive breast cancer.

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Section: Hlx02mentioning

confidence: 99%

Targeting mTOR and Glycolysis in HER2-Positive Breast Cancer

Holloway

Marignani

2021

Cancers

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“…Currently, the drugs used to target HER2 for the treatment of breast cancer primarily include trastuzumab, lapatinib, Pertuzumab and ado-trastuzumab emtansine ( Figueroa-Magalhaes et al, 2014 ; Bartsch and Bergen, 2018 ). Trastuzumab was the first anti-HER2 antibody and has a good therapeutic effect on HER2-positive breast cancer ( Osako et al, 2015 ; Li et al, 2018 ; Zhu et al, 2020 ). Pertuzumab (trade name: Perjeta®) is another HER2 monoclonal antibody that blocks formation of the HER2 dimer and its receptor by binding HER2, inhibiting activation of the PI3K-PKB/Akt signaling pathway, inhibiting the activity of cancer cells, slowing tumor growth, and reducing recurrence rate ( Osako et al, 2015 ; Williams et al, 2017 ; Paek et al, 2019 ).…”

Section: Introductionmentioning

confidence: 99%

“…The production process of biological agents is complex, and any slight difference may cause the final product to fail (Zhang et al, 2020a;Zhang et al, 2020b). Therefore, biosimilars should be comparable with reference preparations in terms of quality, biological activity, safety and efficacy to ensure their safety and effectiveness before they can be approved for marketing (Zhang et al, 2020a;Farahani et al, 2020;Finck et al, 2020;Zhu et al, 2020). It is very important to study the pharmacokinetics (PK), efficacy, safety and immunogenicity of biosimilars (Shin et al, 2020).…”

Section: Introductionmentioning

confidence: 99%

Pharmacokinetics, Immunogenicity and Safety Study for SHR-1309 Injection and Perjeta® in Healthy Chinese Male Volunteers

Cui

Ren

et al. 2021

Front. Pharmacol.

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Objectives: Pertuzumab is a monoclonal antibody for the treatment of breast cancer. The aim of this study was to compare the pharmacokinetics, immunogenicity and safety of the test preparation SHR-1309 injecta and the reference preparation Perjeta® in healthy Chinese male subjects.Methods: In this randomized, double-blind, single dose, two-way, parallel bioequivalence trial, a total of 80 qualified Chinese male subjects were selected and randomly divided into two groups. Each subject was intravenously injected with SHR-1309 or Perjeta®. Blood samples were collected at 21 different time points for pharmacokinetic analysis. In addition, immunogenicity was assessed at five different time points. The safety of the medication was monitored throughout the whole trial.Results: Cmax and AUC0-t were the primary pharmacokinetic parameters. Under a 90% confidence interval, their geometric mean ratios were 98.30 and 88.41% for SHR-1309 injection and Perjeta®, respectively. The geometric mean ratio of secondary pharmacokinetic parameters AUC0-∞ was 88.58%. These evaluation indexes are in the standard range of 80–125%, so SHR-1309 can be considered bioequivalent to Perjeta®. After 1,680 h (day 70) of administration, the two groups had 12 and 13 subjects who produced antidrug antibody (ADA), respectively. The occurrence time and proportion of ADA in SHR-1309 and Perjeta® were similar between subjects, and they had similar immunogenicity. During the entire trial period, there were 71 drug-related adverse reactions in 29 subjects who received SHR-1309 and 61 drug-related adverse reactions in 32 subjects who received Perjeta®. The incidence of adverse reactions between the two drugs was similar.Conclusion: The pharmacokinetic parameters, immunogenicity and safety of the biosimilar SHR-1309 injection produced by Shanghai Hengrui Pharmaceutical Co. Ltd. were similar to the original drug Perjeta® produced by Roche Pharma AG. The two drugs met the bioequivalence evaluation criteria. Therefore, SHR-1309 is bioequivalent to Perjeta®. Clinical trial registration: CTR20200,738.

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“…The availability of Zercepac® changed actuality. Produced by Henlius, Zercepac® is the first biosimilar of trastuzumab and has obtained all the indications that Herceptin® (trastuzumab) has been approved in China due to the pleasure results of clinical trials (NCT02581748, NCT03084237, ; CTR20160526, [ 81 ].,[ 82 ] Up to 2021, 18 biosimilars of trastuzumab and pertuzumab have entered the competition of anti-HER2 biosimilar.…”

Section: Patent Review Of Biosimilar Monoclonal Antibodiesmentioning

confidence: 99%

Biosimilar monoclonal antibodies in China: A patent review

Liu

Yang

et al. 2022

Bioengineered

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Biosimilars play an important role in reducing the burden on patients and increasing the market competition. Biosimilar monoclonal antibodies are currently one of the hotspots of research and development in China with policies support. With the continuous improvement of policies, the enthusiasm for the research and development of biosimilars has increased year by year. The policy requirements in different periods have different degrees of impact on the patent applications of pharmaceutical companies. This review introduces the biosimilar monoclonal antibodies market status and approval process in China, analyzes the patents in this field, and helps pharmaceutical companies protect their intellectual property rights.

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A Phase 1 randomized study compare the pharmacokinetics, safety and immunogenicity of HLX02 to reference CN- and EU-sourced trastuzumab in healthy subjects

Cited by 15 publications

References 18 publications

Targeting mTOR and Glycolysis in HER2-Positive Breast Cancer

Targeting mTOR and Glycolysis in HER2-Positive Breast Cancer

Pharmacokinetics, Immunogenicity and Safety Study for SHR-1309 Injection and Perjeta® in Healthy Chinese Male Volunteers

Biosimilar monoclonal antibodies in China: A patent review

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