A randomized phase I clinical trial comparing the pharmacokinetic, safety, and immunogenicity of potential biosimilar recombinant human HER2 monoclonal antibody for injection and trastuzumab in healthy Chinese adults

Wang, Jiaxue; Niu, Suping; Dong, Wanli; Li, Wei; Ou, Lun; Zhang, Tan; Zhang, Liangbi; Nie, Xiaoyan; Wang, Qian; Shen, Tiantian; Wang, Qi; Lin, Xia; Liu, Gang; Jin, Jiting; Zheng, Qingshan; Song, Haifeng; Fang, Yi

doi:10.1080/13543784.2020.1770226

Cited by 9 publications

(10 citation statements)

References 22 publications

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“…In this study, ADA was detected for the first time at 71st day after administration, the incidence of ADA in the two drugs was 30.0 and 32.5%, respectively. Compared to similar antibody drugs in phase I clinical trials, the positive rate of ADA was similar (Wang et al, 2020;Smolen et al, 2021). Subjects who were ADA positive were followed up for 24 months.…”

Section: Discussionmentioning

confidence: 99%

“…Around 25–30% of breast cancer patients exhibit overexpression of HER2 ( Yu et al, 2017 ). In China, 27–49% of breast cancer patients are HER2-positive ( Wang et al, 2020 ). HER2-overexpressing breast cancer has a poor prognosis and often relapses ( Swain et al, 2015 ; Wang et al, 2020 ), representing an important public health problem in many countries.…”

Section: Introductionmentioning

confidence: 99%

“…In China, 27–49% of breast cancer patients are HER2-positive ( Wang et al, 2020 ). HER2-overexpressing breast cancer has a poor prognosis and often relapses ( Swain et al, 2015 ; Wang et al, 2020 ), representing an important public health problem in many countries. Currently, HER2 is recognized as one of the most common targets in breast cancer treatment ( Yu et al, 2017 ).…”

Section: Introductionmentioning

confidence: 99%

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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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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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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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“…As análises feitas a partir da combinação entre Doxorrubicina (Dox) e Trastuzumab sugerem que esse primeiro quimioterápico, pertencente à classe das antraciclinas, afeta os cardiomiócitos utilizando mecanismos equivalentes ao das células cancerígenas, induzindo dano ao DNA de cardiomiócitos e ativando a formação de matriz extracelular (Zhang, et al, 2020). O Trastuzumab, por sua vez, promove o silenciamento do gene ERBB2, conduzindo a morte de cardiomiócitos por formação de espécies reativas de oxigênio (ROS).…”

Section: Cardiotoxicidade Induzida Pela Associação Entre Quimioterápi...unclassified

“…A análise sistemática proposta por Battisti e colaboradores também demonstrou que mulheres com mais de 65 anos, com HER-2/neu hiperexpresso no tecido mamário, costumam não obter melhora de sobrevida através do uso de capecitabina isolada (Battisti, et al, 2021). Em outra avaliação, o uso de Trastuzumab, além de ser potencial indutor de IC congestiva, esteve associado ao risco de hipotensão ortostática em idosas, aumentando, portanto, o risco de traumas e quedas associados, eventos considerados como agravantes de prognóstico (Wang, et al, 2020).…”

Section: Classificação Fatores De Risco E Agravos Relacionados à Insu...unclassified

Insuficiência cardíaca induzida pelo tratamento quimioterápico do câncer de mama HER-2 Positivo: uma revisão de escopo

Santos¹,

Parreira²,

Júnior

et al. 2022

RSD

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O câncer de mama corresponde a neoplasia que mais afeta mulheres em todo mundo. Dentre os tratamentos mais consagrados para essa patologia, e principalmente para o subtipo imunohistoquímico com hiperexpressão da proteína Her-2, inclui-se a utilização de quimioterápicos, sobretudo antibióticos antineoplásicos e drogas monoclonais. Contudo, essas terapias podem induzir eventos de cardiotoxicidade e insuficiência cardíaca. O presente estudo objetiva avaliar os aspectos relacionados ao desenvolvimento da insuficiência cardíaca decorrente do tratamento quimioterápico para o câncer de mama Her-2 positivo. Para essa Revisão de Escopo, realizada através das plataformas PubMed e Science Direct entre 2020 e 2022, os descritores eleitos foram ‘’Heart Failure’’,‘’Breast Cancer’’, ‘’Her-2’’ e ‘’Ejection Fraction’’, associados ao operador booleano ‘’AND’’. Os critérios de inclusão consistiram em 1) ensaios clínicos, testes controlados e aleatórios, revisões e meta-análises; 2) trabalhos sobre a indução da insuficiência cardíaca decorrente do tratamento para o câncer de mama Her-2 positivo, 3) estudos que avaliaram os danos da cardiotoxicidade e 4) artigos acerca do manejo clínico da insuficiência cardíaca. Os critérios de exclusão consistiram em inadequações ao tema, relatos de casos e estudos com animais, além de textos fora do limite temporal. Observou-se que a insuficiência cardíaca após o uso de quimioterapia atuou como preditor de morbimortalidade grave. Os eventos adversos decorrentes do uso de antineoplásicos para a neoplasia mamária Her-2 positiva variaram desde queda na fração de ejeção, até quadros de morte súbita. A descontinuação desses medicamentos ainda permanece como tópico a ser elucidado, bem como a aplicação das estratégias de cardioproteção.

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A Randomized, Single‐dose, Phase I Clinical Comparison of a Trastuzumab Biosimilar With a Reference Trastuzumab Formulation in Healthy Chinese Male Volunteers

Jia

Zhao

et al. 2022

Clinical Pharm in Drug Dev

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The test drug, a recombinant humanized monoclonal antibody, is a biosimilar candidate for the reference drug. The purpose of this study was to evaluate the bioequivalence of these two drugs. The study was divided into two parts, a pre‐study and a formal trial. The pre‐study included two subjects who were each given a single intravenous infusion of 6 mg/kg test drug. The formal trial was designed to be a randomized, double‐blind, parallel controlled trial in which 70 subjects were randomly assigned 1:1 to receive either test or reference drug as a single 6 mg/kg intravenous infusion. In the pre‐study, the immunogenicity was negative in both subjects and the safety of the test drug was considered to be good. The two groups in the formal trial had similar demographic characteristics. The 90% confidence interval of geometric mean ratios of area under the serum concentration‐time curve from the time 0 to the time of last quantifiable concentration, area under the serum concentration‐curve from time 0 to infinity, and maximum observed serum concentration between the test group and the reference group fell between 80% and 125% and the bioequivalence was recognized. There was no significant difference in the positive rate of antidrug antibodies. The treatment‐emergent adverse events in the test group were similar to those in the reference group. This study showed that the test drug has similar pharmacokinetics, immunogenicity, and safety to the reference drug in healthy male subjects.

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A randomized phase I clinical trial comparing the pharmacokinetic, safety, and immunogenicity of potential biosimilar recombinant human HER2 monoclonal antibody for injection and trastuzumab in healthy Chinese adults

Cited by 9 publications

References 22 publications

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

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

Insuficiência cardíaca induzida pelo tratamento quimioterápico do câncer de mama HER-2 Positivo: uma revisão de escopo

A Randomized, Single‐dose, Phase I Clinical Comparison of a Trastuzumab Biosimilar With a Reference Trastuzumab Formulation in Healthy Chinese Male Volunteers

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