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Trastuzumab emtansine (T-DM1) is an antibody–drug conjugate (ADC) therapeutic for treatment of human epidermal growth factor receptor 2 (HER2)-positive cancers. The T-DM1 dose product contains a mixture of drug-to-antibody ratio (DAR) moieties whereby the small molecule DM1 is chemically conjugated to trastuzumab antibody. The pharmacokinetics (PK)(More)
PURPOSE Trastuzumab-emtansine (T-DM1) is an antibody-drug conjugate (ADC) comprising the cytotoxic agent DM1 conjugated to trastuzumab with a stable linker. Thrombocytopenia was the dose-limiting toxicity in the phase I study, and grade ≥3 thrombocytopenia occurred in up to 13% of patients receiving T-DM1 in phase III studies. We investigated the mechanism(More)
Delta-like-4 ligand (DLL4) plays an important role in vascular development and is widely expressed on the vasculature of normal and tumor tissues. Anti-DLL4 is a humanized IgG1 monoclonal antibody against DLL4. The purpose of these studies was to characterize the pharmacokinetics (PK), tissue distribution, and anti-tumor efficacy of anti-DLL4 in mice over a(More)
Purpose: Trastuzumab-emtansine (T-DM1) is an antibody– drug conjugate (ADC) comprising the cytotoxic agent DM1 conjugated to trastuzumab with a stable linker. Thrombocytopenia was the dose-limiting toxicity in the phase I study, and grade !3 thrombocytopenia occurred in up to 13% of patients receiving T-DM1 in phase III studies. We investigated the(More)
Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. Running title: The effect of T-DM1 on platelets and megakaryocytes Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. These experiments may impact patient care by increasing our understanding of mechanisms(More)
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