Population Pharmacokinetics of MYL-1402O, a Proposed Biosimilar to Bevacizumab and Reference Product (Avastin?) in Patients with Non-squamous Non-small Cell Lung Cancer

Background and Objectives MYL-1402O is a bevacizumab (Avastin (R)) biosimilar. Pharmacokinetic and safety similarity of MYL-1402O and reference Avastin (R) authorized in the European Union (EU-Avastin (R)) and the US (US-Avastin (R)) was demonstrated in healthy subjects (phase I, NCT02469987). The key objectives of this study were to establish a population pharmacokinetic (PopPK) model on pooled data from the phase I and phase III clinical studies to assess pharmacokinetic linearity of MYL-1402O and Avastin (R) across dose ranges, to assess the pharmacokinetic similarity of MYL-1402O and Avastin (R) in patients with non-squamous non-small cell lung cancer (nsNSCLC), and to explore potential covariates to account for systematic sources of variability in bevacizumab exposure.Methods Efficacy and safety of MYL-1402O compared with EU-Avastin (R) was investigated in a multicenter, double-blind, randomized, parallel-group study in patients with stage IV nsNSCLC (phase III, NCT04633564). PopPK models were developed using a nonlinear mixed effects approach (NONMEM (R) 7.3.0).Results The pharmacokinetics of Avastin (R) and MYL-1402O were adequately described with a two-compartment linear model. Fourteen covariates were found to be statistically significant predictors of bevacizumab pharmacokinectics. The impact of each covariate on area under the concentration-time curve, half-life, and maximum plasma concentration was modest, and ranges were similar between the treatment groups, MYL-1402O and EU-Avastin (R), in patients with nsNSCLC. The pharmacokinectics of bevacizumab appeared to be linear.Conclusions PopPK analysis revealed no significant differences between pharmacokinetics of MYL-1402O and Avastin (R) in patients with nsNSCLC. The developed PopPK model was considered robust, as it adequately described bevacizumab pharmacokinetics in healthy participants and nsNSCLC patients.