Clinical Pharmacokinetics and Pharmacodynamics of Atezolizumab in Metastatic Urothelial Carcinoma

被引:125
作者
Stroh, M. [1 ]
Winter, H. [1 ]
Marchand, M. [2 ]
Claret, L. [2 ]
Eppler, S. [1 ]
Ruppel, J. [1 ]
Abidoye, O. [1 ]
Teng, S. L. [1 ]
Lin, W. T. [1 ]
Dayog, S. [1 ]
Bruno, R. [2 ]
Jin, J. [1 ]
Girish, S. [1 ]
机构
[1] Genentech Inc, San Francisco, CA 94080 USA
[2] Pharsight Consulting Serv, Marseille, France
关键词
MONOCLONAL-ANTIBODY; CANCER; MPDL3280A;
D O I
10.1002/cpt.587
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
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 IIMUC 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.
引用
收藏
页码:305 / 312
页数:8
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