LAUSR

to quantify sources of variability, including body size effects, on ADC and monomethyl auristatin E (MMAE) PK in paediatric pts with classical Hodgkin lymphoma (cHL). Methods: POPPK base-models were based on previously reported models. A full model was developed including all statistically-relevant prespecified covariate effects; a final model was chosen by retaining only the significant covariate effects (p<0.001). Model parameters were estimated using NONMEM (v7.3). The final model was used to simulate mg/kg or body surface area (BSA)-based dosing scenarios in paediatric pts to inform selection of posology that provides exposures matching those achieved in adults with weight-based (mg/kg) dosing. Results: Data were collected from 84 pts with a median age of 25.7 years (range 7–87, 34 of whom [40.5%] were aged <18 years), median weight of 67 kg (range 21–154), and median BSA of 1.8 m (range 0.86–2.8). ADC PK was described by a linear 3-compartment model with zero-order input and first-order elimination. In covariate analyses, BSA was the best predictor of body size effects on ADC PK, and was a strong predictor of clearance (CL), V1, and V3; anti-drug antibodies were predictors of ADC CL. POPPK simulations of 1.8 mg/kg Q3W dosing found lower AUC values in small/moderate body weight paediatric pts (<28 kg/ 28–49 kg) compared with larger paediatric/adult pts (50–100 kg). Dosing at 71.5 mg/m had comparable AUC values across all body weight ranges and a similar AUC to the reference scenario of 1.8 mg/kg dosing in the 50–100 kg group. Simulations of low dose Q2W BV dosing (1.2 mg/kg and 47.7 mg/m), found similar results to the adult Q3W 1.8 mg/kg regimen. These results provide a hypothesis to further evaluate the relative performance of BSA-based vs weight-based dosing as an approach to minimize inter-patient variability in pediatric PK. AUC distributions with BSA-based dosing at 47.7 mg/macross the weight ranges (including the <28 kg group) were similar to those achieved in the adult weight range (50–100 kg) with body weight-based dosing at 1.2 mg/kg (Figure). POPPK results for MMAE will be presented. Conclusions: ADC POPPK results support the evaluation of a BSAbased dosing regimen (48 mg/m Q2W) as an alternative dosing option in a phase 1/2 study to evaluate frontline A+AVD efficacy and safety in paediatric cHL pts (NCT02979522). Model-informed approaches to pediatric oncology drug development enable dose selection aimed at minimizing inter-pt variability during clinical evaluation of safety and efficacy.