A phase I study with adecatumumab, a human antibody directed against epithelial cell adhesion molecule, in hormone refractory prostate cancer patients.

ABSTRACT

AIM OF THE STUDY Adecatumumab (also known as MT201) is a human recombinant IgG1 monoclonal antibody binding with low affinity to epithelial cell adhesion molecule (EpCAM). To explore safety, pharmacokinetics and pharmacodynamics of adecatumumab, a phase I trial in patients with hormone refractory prostate cancer (HRPC) was performed. METHODS: Twenty patients were treated with two adecatumumab infusions on days 0 and 14 in cohorts with doses of ten up to 262 mg/m2. RESULTS: Adecatumumab was well tolerated at all doses tested, and no maximum tolerated dose reached. Most adverse events were mild or moderate with pyrexia and nausea being most frequent. The highest dose of adecatumumab induced shortly after infusion robust and transient increases of TNF-alpha serum levels. At all doses, significant transient declines of peripheral natural killer cells were observed shortly after antibody infusions. Adecatumumab had a serum half-life of 15 days, and immune responses to the antibody were not detected. CONCLUSIONS: A benign safety profile, long serum half-life and low immunogenicity do warrant further exploration of adecatumumab for treatment of EpCAM-expressing neoplasia.