Clinical Pharmacokinetics and Pharmacodynamics of Atezolizumab in Metastatic Urothelial Carcinoma.
Clin Pharmacol Ther
; 102(2): 305-312, 2017 Aug.
Article
em En
| MEDLINE
| ID: mdl-27981577
ABSTRACT
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.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Neoplasias Urológicas
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Anticorpos Monoclonais
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Antineoplásicos
Limite:
Animals
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Humans
Idioma:
En
Revista:
Clin Pharmacol Ther
Ano de publicação:
2017
Tipo de documento:
Article
País de afiliação:
Estados Unidos