Clinical Pharmacokinetics and Pharmacodynamics of Atezolizumab in Metastatic Urothelial Carcinoma
Atezolizumab, a humanized immunoglobulin G1 (IgG1) monoclonal antibody targeting human programmed death‐ligand 1 (PD‐L1), is US Food and Drug Administration (FDA) approved in metastatic urothelial carcinoma (MUC) and is being investigated in various malignancies. This analysis based upon 906 patient...
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| Veröffentlicht in: | Clinical pharmacology and therapeutics 2017-08, Vol.102 (2), p.305-312 |
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| creator | Stroh, M Winter, H Marchand, M Claret, L Eppler, S Ruppel, J Abidoye, O Teng, SL Lin, WT Dayog, S Bruno, R Jin, J Girish, S |
| description | Atezolizumab, a humanized immunoglobulin G1 (IgG1) monoclonal antibody targeting human programmed death‐ligand 1 (PD‐L1), is US Food and Drug Administration (FDA) approved in metastatic urothelial carcinoma (MUC) and is being investigated in various malignancies. This analysis based upon 906 patients from two phase I and one phase II MUC studies, is the first report of the clinical pharmacokinetics (PK) and pharmacodynamics (PD) of atezolizumab. Atezolizumab exhibited linear PK over a dose range of 1–20 mg/kg, including the labeled 1,200 mg dose. The clearance, volume of distribution, and terminal half‐life estimates from population pharmacokinetic (PopPK) analysis of 0.200 L/day, 6.91 L, and 27 days, respectively, were as expected for an IgG1. Exposure‐response analyses did not identify statistically significant relationships with either objective response rate or adverse events of grades 3–5 or of special interest. None of the statistically significant covariates from PopPK (body weight, gender, antitherapeutic antibody, albumin, and tumor burden) would require dose adjustment. |
| doi_str_mv | 10.1002/cpt.587 |
| format | Article |
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This analysis based upon 906 patients from two phase I and one phase II MUC studies, is the first report of the clinical pharmacokinetics (PK) and pharmacodynamics (PD) of atezolizumab. Atezolizumab exhibited linear PK over a dose range of 1–20 mg/kg, including the labeled 1,200 mg dose. The clearance, volume of distribution, and terminal half‐life estimates from population pharmacokinetic (PopPK) analysis of 0.200 L/day, 6.91 L, and 27 days, respectively, were as expected for an IgG1. Exposure‐response analyses did not identify statistically significant relationships with either objective response rate or adverse events of grades 3–5 or of special interest. None of the statistically significant covariates from PopPK (body weight, gender, antitherapeutic antibody, albumin, and tumor burden) would require dose adjustment.</description><identifier>ISSN: 0009-9236</identifier><identifier>EISSN: 1532-6535</identifier><identifier>DOI: 10.1002/cpt.587</identifier><identifier>PMID: 27981577</identifier><language>eng</language><publisher>United States</publisher><subject>Animals ; Antibodies, Monoclonal - pharmacokinetics ; Antibodies, Monoclonal - therapeutic use ; Antibodies, Monoclonal, Humanized - pharmacokinetics ; Antibodies, Monoclonal, Humanized - therapeutic use ; Antineoplastic Agents - pharmacokinetics ; Antineoplastic Agents - therapeutic use ; Dose-Response Relationship, Drug ; Humans ; Urologic Neoplasms - drug therapy ; Urologic Neoplasms - metabolism</subject><ispartof>Clinical pharmacology and therapeutics, 2017-08, Vol.102 (2), p.305-312</ispartof><rights>2016 American Society for Clinical Pharmacology and Therapeutics</rights><rights>2016 American Society for Clinical Pharmacology and Therapeutics.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c3837-5aa62ec74259e916455d433e7e48800a36a7c3069365065825527bd615bb7dc3</citedby><cites>FETCH-LOGICAL-c3837-5aa62ec74259e916455d433e7e48800a36a7c3069365065825527bd615bb7dc3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2Fcpt.587$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Fcpt.587$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,776,780,1411,27901,27902,45550,45551</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/27981577$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Stroh, M</creatorcontrib><creatorcontrib>Winter, H</creatorcontrib><creatorcontrib>Marchand, M</creatorcontrib><creatorcontrib>Claret, L</creatorcontrib><creatorcontrib>Eppler, S</creatorcontrib><creatorcontrib>Ruppel, J</creatorcontrib><creatorcontrib>Abidoye, O</creatorcontrib><creatorcontrib>Teng, SL</creatorcontrib><creatorcontrib>Lin, WT</creatorcontrib><creatorcontrib>Dayog, S</creatorcontrib><creatorcontrib>Bruno, R</creatorcontrib><creatorcontrib>Jin, J</creatorcontrib><creatorcontrib>Girish, S</creatorcontrib><title>Clinical Pharmacokinetics and Pharmacodynamics of Atezolizumab in Metastatic Urothelial Carcinoma</title><title>Clinical pharmacology and therapeutics</title><addtitle>Clin Pharmacol Ther</addtitle><description>Atezolizumab, a humanized immunoglobulin G1 (IgG1) monoclonal antibody targeting human programmed death‐ligand 1 (PD‐L1), is US Food and Drug Administration (FDA) approved in metastatic urothelial carcinoma (MUC) and is being investigated in various malignancies. 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| source | Wiley Online Library - AutoHoldings Journals; MEDLINE |
| subjects | Animals Antibodies, Monoclonal - pharmacokinetics Antibodies, Monoclonal - therapeutic use Antibodies, Monoclonal, Humanized - pharmacokinetics Antibodies, Monoclonal, Humanized - therapeutic use Antineoplastic Agents - pharmacokinetics Antineoplastic Agents - therapeutic use Dose-Response Relationship, Drug Humans Urologic Neoplasms - drug therapy Urologic Neoplasms - metabolism |
| title | Clinical Pharmacokinetics and Pharmacodynamics of Atezolizumab in Metastatic Urothelial Carcinoma |
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