Phase I study of the novel fully human monoclonal antibody MT201, directed against epithelial cellular adhesion molecule (Ep-CAM), in patients with hormone-refractory prostate cancer (HRPC)

Abstract

2600 Background: MT201 is a novel, fully human IgG1 monoclonal antibody directed against human epithelial cellular adhesion molecule (Ep-CAM), which is expressed on a wide variety of tumor cells. For breast cancer, it has been shown that high expression levels of Ep-CAM on tumor samples correlates with reduced disease-free and overall survival. MT201 has an intermediate affinity towards the Ep-CAM antigen (1.4 x 10–7 M). A wide variety of tumor cell lines are killed by MT201-mediated antibody-dependent cellular cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC). Moreover, primary prostate and ovarian cancer cells were killed by MT201 using either exogenous peripheral blood mononuclear cells (PBMCs) as effector cells or endogenous effector cells present in the tumor cell homogenate. Methods: Twenty patients were treated in a dose-escalation phase I study with two separate infusions of MT201 on study days 1 and 15 and were followed for 42 days. Doses ranged from 10 mg/m2 to 262 mg/m2. Tolerability, maximum tolerated dose (MTD), and pharmacokinetics were endpoints. Results: MT201 was generally well tolerated at all doses tested. A total of 120 adverse events regardless of relationship with study drug were reported in 19 (95%) patients during the treatment and the 28-day safety follow-up period. Most were mild or moderate, none was severe or treatment-limiting. No dose-limiting toxicities were reported and the MTD was not determined. No antibodies against MT201 were detected. A long half-life of 15 days was observed. Conclusions: MT201 might represent a new treatment opportunity for patients with epithelial cancers that overexpress Ep-CAM. Due to its favourable safety profile, the compound might be suitable even for patients at early stages in their tumor development. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Micromet AG