Population Pharmacokinetics of Brentuximab Vedotin in Adult and Pediatric Patients With Relapsed/Refractory Hematologic Malignancies: Model‐Informed Hypothesis Generation for Pediatric Dosing Regimens

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Abstract
Prior pharmacokinetic (PK) analyses of the antibody‐drug conjugate (ADC) brentuximab vedotin (1.8 mg/kg every 3 weeks) in pediatric patients with relapsed/refractory hematologic malignancies found that patients aged 2 (range, 0.87‐2.81 m2). ADC PK was described by a linear 3‐compartment model with zero‐order input and first‐order elimination. POPPK modeling indicated that dosing brentuximab vedotin at 1.8 mg/kg every 3 weeks or 1.2 mg/kg every 2 weeks resulted in lower ADC AUC values in small/moderate‐sized pediatric patients (2 every 3 weeks and 47.7 mg/m2 every 2 weeks was predicted to achieve comparable AUC values across all body weight ranges and a similar AUC to that in the 50‐ to 100‐kg group at the standard doses of 1.8 mg/kg every 3 weeks and 1.2 mg/kg every 2 weeks, respectively. These results have generated a hypothesis to support evaluation of brentuximab vedotin at 48 mg/m2 every 2 weeks in combination with adriamycin, vinblastine, and dacarbazine chemotherapy in an ongoing pediatric trial in frontline Hodgkin lymphoma (NCT02979522).

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