Exposure-Efficacy Analysis of Antibody-Drug Conjugates Delivering an Excessive Level of Payload to Tissues (original) (raw)

2019, Drug Metabolism and Disposition

Introduction: 634 Results: 2210 Discussion: 1710 Abbreviations: ADC, antibody-drug conjugate; AUC, area under amount or concentration versus time curve, C max , maximum concentration; C tumor , payload concentration in tumor; DAR, drug-to-antibody ratio; DMx, maytansinoid DM1, DM3, or DM4; DNA, deoxy nucleic acid; HC, heavy chain of an antibody; IV, intravenous dosing; LC/MS, liquid chromatography tandem mass spectrometry; LC, light chain of an antibody; mAb, monoclonal antibody; MCC, Maleimidomethyl cyclohexane-1carboxylate; MMAE, monomethyl auristatin E; MRM, multiple reaction monitoring; PBS, phosphate buffer solution; PBD, pyrrolo[2,1-c][1,4]benzodiazepine-dimer; PBPK, physiology-based pharmacokinetic modeling; PK, pharmacokinetics; R, payload concentration ratio in tumor over tissue; SM, small molecule drug; Tab, total antibody (could include DAR2, DAR1 and DAR0 species for ADCs in this study); TGI rel , relative tumor growth inhibition This article has not been copyedited and formatted. The final version may differ from this version.