Joel S Owen, Russell J Rackley, Matthew A Hummel, Stefan Roepcke, Hannah Huang, Mark Liu, Tazeen A Idris, Sundara Moorthi Nainar Murugesan, Ashwani Marwah, Subramanian Loganathan, Gopinath Ranganna, Abhijit Barve, Cornelius F Waller, Mark A Socinski
{"title":"非鳞状非小细胞肺癌癌症患者中拟议的贝伐单抗生物类似物和参考产品（Avastin®）MYL-1402O的群体药代动力学。","authors":"Joel S Owen, Russell J Rackley, Matthew A Hummel, Stefan Roepcke, Hannah Huang, Mark Liu, Tazeen A Idris, Sundara Moorthi Nainar Murugesan, Ashwani Marwah, Subramanian Loganathan, Gopinath Ranganna, Abhijit Barve, Cornelius F Waller, Mark A Socinski","doi":"10.1007/s13318-023-00855-3","DOIUrl":null,"url":null,"abstract":"<p><strong>Background and objectives: </strong>MYL-1402O is a bevacizumab (Avastin<sup>®</sup>) biosimilar. Pharmacokinetic and safety similarity of MYL-1402O and reference Avastin<sup>®</sup> authorized in the European Union (EU-Avastin<sup>®</sup>) and the US (US-Avastin<sup>®</sup>) was demonstrated in healthy subjects (phase I, NCT02469987). The key objectives of this study were to establish a population pharmacokinetic (PopPK) model on pooled data from the phase I and phase III clinical studies to assess pharmacokinetic linearity of MYL-1402O and Avastin<sup>®</sup> across dose ranges, to assess the pharmacokinetic similarity of MYL-1402O and Avastin<sup>®</sup> in patients with non-squamous non-small cell lung cancer (nsNSCLC), and to explore potential covariates to account for systematic sources of variability in bevacizumab exposure.</p><p><strong>Methods: </strong>Efficacy and safety of MYL-1402O compared with EU-Avastin<sup>®</sup> was investigated in a multicenter, double-blind, randomized, parallel-group study in patients with stage IV nsNSCLC (phase III, NCT04633564). PopPK models were developed using a nonlinear mixed effects approach (NONMEM<sup>®</sup> 7.3.0).</p><p><strong>Results: </strong>The pharmacokinetics of Avastin<sup>®</sup> and MYL-1402O were adequately described with a two-compartment linear model. Fourteen covariates were found to be statistically significant predictors of bevacizumab pharmacokinectics. The impact of each covariate on area under the concentration-time curve, half-life, and maximum plasma concentration was modest, and ranges were similar between the treatment groups, MYL-1402O and EU-Avastin<sup>®</sup>, in patients with nsNSCLC. The pharmacokinectics of bevacizumab appeared to be linear.</p><p><strong>Conclusions: </strong>PopPK analysis revealed no significant differences between pharmacokinetics of MYL-1402O and Avastin<sup>®</sup> in patients with nsNSCLC. The developed PopPK model was considered robust, as it adequately described bevacizumab pharmacokinetics in healthy participants and nsNSCLC patients.</p>","PeriodicalId":11939,"journal":{"name":"European Journal of Drug Metabolism and Pharmacokinetics","volume":null,"pages":null},"PeriodicalIF":1.9000,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Population Pharmacokinetics of MYL-1402O, a Proposed Biosimilar to Bevacizumab and Reference Product (Avastin<sup>®</sup>) in Patients with Non-squamous Non-small Cell Lung Cancer.\",\"authors\":\"Joel S Owen, Russell J Rackley, Matthew A Hummel, Stefan Roepcke, Hannah Huang, Mark Liu, Tazeen A Idris, Sundara Moorthi Nainar Murugesan, Ashwani Marwah, Subramanian Loganathan, Gopinath Ranganna, Abhijit Barve, Cornelius F Waller, Mark A Socinski\",\"doi\":\"10.1007/s13318-023-00855-3\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background and objectives: </strong>MYL-1402O is a bevacizumab (Avastin<sup>®</sup>) biosimilar. Pharmacokinetic and safety similarity of MYL-1402O and reference Avastin<sup>®</sup> authorized in the European Union (EU-Avastin<sup>®</sup>) and the US (US-Avastin<sup>®</sup>) was demonstrated in healthy subjects (phase I, NCT02469987). The key objectives of this study were to establish a population pharmacokinetic (PopPK) model on pooled data from the phase I and phase III clinical studies to assess pharmacokinetic linearity of MYL-1402O and Avastin<sup>®</sup> across dose ranges, to assess the pharmacokinetic similarity of MYL-1402O and Avastin<sup>®</sup> in patients with non-squamous non-small cell lung cancer (nsNSCLC), and to explore potential covariates to account for systematic sources of variability in bevacizumab exposure.</p><p><strong>Methods: </strong>Efficacy and safety of MYL-1402O compared with EU-Avastin<sup>®</sup> was investigated in a multicenter, double-blind, randomized, parallel-group study in patients with stage IV nsNSCLC (phase III, NCT04633564). PopPK models were developed using a nonlinear mixed effects approach (NONMEM<sup>®</sup> 7.3.0).</p><p><strong>Results: </strong>The pharmacokinetics of Avastin<sup>®</sup> and MYL-1402O were adequately described with a two-compartment linear model. Fourteen covariates were found to be statistically significant predictors of bevacizumab pharmacokinectics. The impact of each covariate on area under the concentration-time curve, half-life, and maximum plasma concentration was modest, and ranges were similar between the treatment groups, MYL-1402O and EU-Avastin<sup>®</sup>, in patients with nsNSCLC. The pharmacokinectics of bevacizumab appeared to be linear.</p><p><strong>Conclusions: </strong>PopPK analysis revealed no significant differences between pharmacokinetics of MYL-1402O and Avastin<sup>®</sup> in patients with nsNSCLC. The developed PopPK model was considered robust, as it adequately described bevacizumab pharmacokinetics in healthy participants and nsNSCLC patients.</p>\",\"PeriodicalId\":11939,\"journal\":{\"name\":\"European Journal of Drug Metabolism and Pharmacokinetics\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":1.9000,\"publicationDate\":\"2023-11-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"European Journal of Drug Metabolism and Pharmacokinetics\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1007/s13318-023-00855-3\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2023/10/4 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q3\",\"JCRName\":\"PHARMACOLOGY & PHARMACY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"European Journal of Drug Metabolism and Pharmacokinetics","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1007/s13318-023-00855-3","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2023/10/4 0:00:00","PubModel":"Epub","JCR":"Q3","JCRName":"PHARMACOLOGY & PHARMACY","Score":null,"Total":0}
Population Pharmacokinetics of MYL-1402O, a Proposed Biosimilar to Bevacizumab and Reference Product (Avastin®) in Patients with Non-squamous Non-small Cell Lung Cancer.
Background and objectives: MYL-1402O is a bevacizumab (Avastin®) biosimilar. Pharmacokinetic and safety similarity of MYL-1402O and reference Avastin® authorized in the European Union (EU-Avastin®) and the US (US-Avastin®) was demonstrated in healthy subjects (phase I, NCT02469987). The key objectives of this study were to establish a population pharmacokinetic (PopPK) model on pooled data from the phase I and phase III clinical studies to assess pharmacokinetic linearity of MYL-1402O and Avastin® across dose ranges, to assess the pharmacokinetic similarity of MYL-1402O and Avastin® in patients with non-squamous non-small cell lung cancer (nsNSCLC), and to explore potential covariates to account for systematic sources of variability in bevacizumab exposure.
Methods: Efficacy and safety of MYL-1402O compared with EU-Avastin® was investigated in a multicenter, double-blind, randomized, parallel-group study in patients with stage IV nsNSCLC (phase III, NCT04633564). PopPK models were developed using a nonlinear mixed effects approach (NONMEM® 7.3.0).
Results: The pharmacokinetics of Avastin® and MYL-1402O were adequately described with a two-compartment linear model. Fourteen covariates were found to be statistically significant predictors of bevacizumab pharmacokinectics. The impact of each covariate on area under the concentration-time curve, half-life, and maximum plasma concentration was modest, and ranges were similar between the treatment groups, MYL-1402O and EU-Avastin®, in patients with nsNSCLC. The pharmacokinectics of bevacizumab appeared to be linear.
Conclusions: PopPK analysis revealed no significant differences between pharmacokinetics of MYL-1402O and Avastin® in patients with nsNSCLC. The developed PopPK model was considered robust, as it adequately described bevacizumab pharmacokinetics in healthy participants and nsNSCLC patients.
期刊介绍：
Hepatology International is a peer-reviewed journal featuring articles written by clinicians, clinical researchers and basic scientists is dedicated to research and patient care issues in hepatology. This journal focuses mainly on new and emerging diagnostic and treatment options, protocols and molecular and cellular basis of disease pathogenesis, new technologies, in liver and biliary sciences.
Hepatology International publishes original research articles related to clinical care and basic research; review articles; consensus guidelines for diagnosis and treatment; invited editorials, and controversies in contemporary issues. The journal does not publish case reports.
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