Ado-trastuzumab Emtansine (T-DM1): An Antibody-Drug Conjugate (ADC) for HER2-Positive Breast Cancer

作者：Lambert, John M.^*; Chari, Ravi V. J.

来源：Journal of Medicinal Chemistry, 2014, 57(16): 6949-6964.

DOI：10.1021/jm500766w

• PHASE-II
• PHARMACOKINETIC MODEL
• MONOCLONAL-ANTIBODY
• TUMOR INHIBITORS
• PLUS DOCETAXEL
• THERAPY
• HER2
• MAYTANSINOIDS
• MECHANISM
• HERCEPTIN

Ado-trastuzumab emtansine (T-DM1) is an antibody drug conjugate that combines the antitumor properties of the humanized anti-human epidermal growth factor receptor 2 (HER2) antibody, trastuzumab, with the maytansinoid, DM1, a potent microtubule-disrupting agent, joined by a stable linker. Upon binding to HER2, the conjugate is internalized via receptor-mediated endocytosis, and an active derivative of DM1 is subsequently released by proteolytic degradation of the antibody moiety within the lysosome. Initial clinical evaluation led to a phase HI trial in advanced HER2-positive breast cancer patients who had relapsed after prior treatment with trastuzumab and a taxane, which showed that T-DM1 significantly prolonged progression-free and overall survival with less toxicity than lapatinib plus capecitabine. In 2013, T-DM1 received FDA approval for the treatment of patients with HER2-positive metastatic breast cancer who had previously received trastuzumab and a taxane, separately or in combination, the first ADC to receive full approval based on a randomized study.

• 出版日期2014-8-28