Avelumab Dose Selection for Clinical Studies in Pediatric Patients with Solid Tumors

Background and Objective A phase I/II trial evaluated the safety, antitumor activity, and pharmacokinetics of avelumab (anti-PD-L1 antibody) in pediatric patients with refractory/relapsed solid tumors (NCT03451825). This study aimed to inform avelumab dose selection in pediatric populations using population pharmacokinetic modeling and simulations. Methods Patients aged Results Pharmacokinetic parameters from 21 patients who received avelumab 10 mg/kg (n = 6) or 20 mg/kg (n = 15) were analyzed. Patients had a wide range of weights and ages (medians, 37.3 kg and 12 years). Exposures with 10-mg/kg dosing were lower vs adult dosing, particularly in patients weighing < 40 kg, whereas 20-mg/kg dosing achieved or exceeded adult exposures, irrespective of body weight. A two-compartment linear model with time-varying clearance using body weight as a covariate, with the frequentist prior approach, best described pediatric data. In this model, optimal overlap in exposure with adult data was achieved with 800 mg every 2 weeks for patients aged >= 12 years and weighing >= 40 kg, and 15 mg/kg every 2 weeks for patients aged Conclusions Based on exposure matching, the recommended doses for further avelumab studies, including combination studies, are 15 mg/kg every 2 weeks for pediatric patients aged < 12 years or weighing < 40 kg and the adult flat dose of 800 mg every 2 weeks for pediatric patients aged >= 12 years and weighing >= 40 kg.