Population pharmacokinetics, exposure-safety, and immunogenicity of atezolizumab in pediatric and young adult patients with cancer

Abstract

BackgroundThe iMATRIX-atezolizumab study was a phase I/II, multicenter, open-label study designed to assess the safety and pharmacokinetics of atezolizumab in pediatric and young adult patients. We describe the pharmacokinetics (PK), exposure-safety, and immunogenicity of atezolizumab in pediatric and young adults with metastatic solid tumors or hematologic malignancies enrolled in this study.MethodsPatients aged <\u200918\u2009years (n\xa0=\u200969) received a weight-adjusted dose of atezolizumab (15\u2009mg/kg every 3\u2009weeks [q3w]; maximum 1200\u2009mg); those aged ≥ 18\u2009years (n\xa0=\u200918) received a flat dose (1200\u2009mg q3w). A prior two-compartment intravenous infusion input adult population-PK (popPK) model of atezolizumab was used as a basis to model pediatric data.ResultsA total of 431 atezolizumab serum concentrations from 87 relapse-refractory pediatric and young adult patients enrolled in the iMATRIX-atezolizumab study were used for the popPK analysis. The dataset comprised predominantly patients aged <\u200918\u2009years, including two infants aged <\u20092\u2009years, with a wide body weight and age range. The clearance and volume of distribution estimates of atezolizumab were 0.217\u2009L/day and 3.01\u2009L, respectively. Atezolizumab geometric mean trough exposures were ~\u200920% lower in pediatric patients versus young adults; this was not clinically meaningful as both groups achieved the target concentration (6\u2009μg/mL). Safety was similar between pediatric and young adult patients with no exposure-safety relationship observed. Limited responses (4/87) precluded an exposure-response assessment on outcomes. A comparable rate (13% vs 11%) of atezolizumab anti-drug antibodies was seen in pediatric and young adult patients.ConclusionsThese findings demonstrate a similar exposure-safety profile of atezolizumab in pediatric and young adult patients, supportive of weight-based dosing in pediatric patients.Trial registrationNCT02541604.