Comparative pharmacokinetics, safety, and tolerability of two sources of ch14.18 in pediatric patients with high-risk neuroblastoma following myeloablative therapy

Cancer Chemotherapy and Pharmacology
Araz MarachelianL Mary Smith

Abstract

Dinutuximab (Unituxin™; ch14.18), a monoclonal antibody against disialoganglioside, improved survival as part of post-consolidation therapy for high-risk neuroblastoma. United Therapeutics Corporation (UTC) assumed ch14.18 production from the National Cancer Institute (NCI); this study evaluates pharmacokinetic comparability, safety, and tolerability of UTC and NCI products. In this randomized, two-sequence crossover study, 28 patients aged ≤8 years with high-risk neuroblastoma received equivalent ch14.18-UTC or ch14.18-NCI doses. Despite comparable protein content, nominal doses differed: 17.5 mg/m(2)/day (ch14.18-UTC) and 25 mg/m(2)/day (ch14.18-NCI). Patients received one product during therapy cycles 1 and 2, the other during cycles 3-5. Ch14.18 pharmacokinetic profile characterization used population modeling (NONMEM(®) version 7.2). A two-compartment model with first-order distribution and elimination processes described pharmacokinetic data. Estimated product parameters were normalized to UTC nominal dose. For pharmacokinetic comparability, the final model was used to estimate exposure ratios (UTC/NCI) and associated 90 % confidence intervals (CIs) for area under the curve from time zero to infinity (AUCinf) and maximum ...Continue Reading

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Citations

Feb 20, 2016·Targeted Oncology·Sheridan M Hoy
Jan 10, 2018·Frontiers in Immunology·Isabel Corraliza-GorjónLeonor Kremer
Nov 16, 2018·Expert Opinion on Drug Safety·Katie L Greenwood, Jennifer H Foster
Apr 10, 2021·Journal of Cellular Physiology·Praveen BhoopathiPaul B Fisher
Jan 29, 2021·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Alice L YuPaul M Sondel
Nov 19, 2021·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Nicholas BirdDonna Ludwinski

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Methods Mentioned

BETA
sandwich immunoassay

Software Mentioned

MLAB
NONMEM

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