Model-informed approach to support pediatric dosing for the pan-PI3K inhibitor copanlisib in children and adolescents with relapsed/refractory solid tumors.

ABSTRACT: Copanlisib is an intravenously administered phosphatidylinositol 3-kinase (PI3K) inhibitor which was investigated in pediatric patients with relapsed/refractory solid tumors. A model-informed approach was undertaken to support and confirm an empirically selected starting dose of 28 mg/m² for pediatric patients ≥1 year old, corresponding to 80% of the adult recommended dose adjusted for body surface area. An adult physiologically based pharmacokinetic (PBPK) model was initially established using copanlisib physicochemical and disposition properties and clinical pharmacokinetics (PK) data and was shown to adequately capture clinical PK across a range of copanlisib doses in adult cancer patients. The adult PBPK model was then extended to the pediatric population through incorporati

SUBMITTER: Morcos PN 

PROVIDER: S-EPMC10339701 | biostudies-literature | 2023 Jul

REPOSITORIES: biostudies-literature