Population pharmacokinetics, efficacy, and safety of moxetumomab pasudotox in patients with relapsed or refractory hairy cell leukaemia.
cancer
modelling and simulation
pharmacokinetic-pharmacodynamic
pharmacokinetics
Journal
British journal of clinical pharmacology
ISSN: 1365-2125
Titre abrégé: Br J Clin Pharmacol
Pays: England
ID NLM: 7503323
Informations de publication
Date de publication:
07 2020
07 2020
Historique:
received:
17
07
2019
revised:
14
12
2019
accepted:
01
02
2020
pubmed:
23
2
2020
medline:
27
7
2021
entrez:
21
2
2020
Statut:
ppublish
Résumé
To characterize the pharmacokinetics (PK) of moxetumomab pasudotox, an anti-CD22 recombinant immunotoxin, in adults with relapsed or refractory hairy cell leukaemia, we examined data from a phase 1 study (Study 1001; n = 49) and from the pivotal clinical study (Study 1053; n = 74). Data from both studies were pooled (n = 123) to develop a population PK model. Covariates included demographics, disease state, liver and kidney function, prior treatment, and antidrug antibodies (ADAs). Exposure-response and exposure-safety were analysed separately by study. A 1-compartment model with linear elimination from the central compartment and 2 clearance (CL) rates was developed. Moxetumomab pasudotox was cleared more rapidly after cycle 1, day 1 (CL Despite a high incidence of immunogenicity with increased clearance, moxetumomab pasudotox demonstrated efficacy in hairy cell leukaemia.
Identifiants
pubmed: 32077130
doi: 10.1111/bcp.14250
pmc: PMC7318999
doi:
Substances chimiques
Antibodies
0
Bacterial Toxins
0
Exotoxins
0
immunotoxin HA22
2NDX4B6N8F
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1367-1376Subventions
Organisme : AstraZeneca
Pays : International
Informations de copyright
© 2020 The British Pharmacological Society.
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