Trastuzumab Emtansine(T-DM1, KadcylaTM, Genentech Inc.) is an antibody-drug conjugate(ADC) that received US FDA approval in 2013 for the treatment of human epidermal growth factor receptor 2 (HER2)-positive cancers.Its primary active metabolite, Lys-MCC-DM 1, was formed in lysosomes after CanAg antigen-mediated endocytosis of T-DM 1.The exposure of Lys-MCCDM1 in tumor directly related to the tumor growth volume (PD).The aim of this study was to utilize T-DM1 as a model ADC to investigate PK profile of individual moiety (DAR0-DAR7) of T-DM1 with DAR 3.4 in human and to predict Lys-MCC-DM1 concentration in tumor and PD profiles.After the reduced and mechanistic PK models were built in Pheonix-NLME software, rat and cynomolgus monkey PK profiles were predicted and then compared with the preclinical data in the previous paper for method validation.