PURPOSE: 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.
METHODS: 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 concentration (C max). All 
comparisons were based on a standardized single-dose regimen (17.5 mg/m(2) over 
10 h).
RESULTS: Final-model pharmacokinetic parameters were similar to previously 
published ch14.18-NCI parameters and comparable for UTC and NCI products. 
Products' systemic exposures were comparable, with 90 % CIs around ratios for 
AUCinf (0.96; 90 % CI 0.88-1.04) and C max (1.04; 90 % CI 0.98-1.11) within 
standard bioequivalence bounds (90 % CI 0.80-1.25). Products' adverse events 
were similar and consistent with those previously reported.
CONCLUSIONS: Equivalent actual ch14.18-UTC and ch14.18-NCI doses produced 
comparable exposures, with no notable safety or tolerability differences.