Model-Based Characterization of the Pharmacokinetics of Pembrolizumab: A Humanized Anti-PD-1 Monoclonal Antibody in Advanced Solid Tumors.
CPT Pharmacometrics Syst Pharmacol
; 6(1): 49-57, 2017 01.
Article
em En
| MEDLINE
| ID: mdl-27863186
ABSTRACT
Pembrolizumab, a potent antibody against programmed death 1 (PD-1) receptor, has shown robust antitumor activity and manageable safety in patients with advanced solid tumors. Its pharmacokinetic (PK) properties were analyzed with population PK modeling using pooled data from the KEYNOTE-001, -002, and -006 studies of patients with advanced melanoma, non-small cell lung cancer (NSCLC), and other solid tumor types. Pembrolizumab clearance was low and the volume of distribution small, as is typical for therapeutic antibodies. Identified effects of sex, baseline Eastern Cooperative Oncology Group performance status, measures of renal and hepatic function, tumor type and burden, and prior ipilimumab treatment on pembrolizumab exposure were modest and lacked clinical significance. Furthermore, simulations demonstrated the model has robust power to detect clinically relevant covariate effects on clearance. These results support the use of the approved pembrolizumab dose of 2 mg/kg every 3 weeks without dose adjustment in a variety of patient subpopulations.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Anticorpos Monoclonais Humanizados
/
Receptor de Morte Celular Programada 1
/
Modelos Biológicos
/
Neoplasias
/
Antineoplásicos
Tipo de estudo:
Clinical_trials
/
Diagnostic_studies
/
Prognostic_studies
Limite:
Humans
Idioma:
En
Revista:
CPT Pharmacometrics Syst Pharmacol
Ano de publicação:
2017
Tipo de documento:
Article
País de afiliação:
Estados Unidos