A first-in-human phase I study of MORAb-004 (M4), a humanized monoclonal antibody recognizing endosialin (TEM-1), in patients with solid tumors.

3016 Background: Endosialin (TEM-1) is a membrane glycoprotein on the cell surface of activated mesenchymal cells (e.g. pericytes, fibroblasts and mesenchymal tumor cells) and on a subset of human cancers. It is involved in the development of tumor vasculature, stromal/tumor organization and PDGFRb signaling. M4 is a humanized IgG monoclonal antibody which targets TEM-1. Preclinical studies suggest that M4 may have single agent activity via inhibition of the tumor microenvironment and by direct effects on tumors expressing this target. Methods: A phase I dose escalation study in patients (pts) with advanced solid tumors was conducted to evaluate the safety, pharmacokinetic profile and preliminary efficacy of M4 administered intravenously on a weekly schedule; final results are presented. Results: 36 pts refractory to therapy were treated at 10 dose levels (0.0625 to 16 mg/kg administered i.v. on a weekly schedule). Drug-related adverse events (AE) observed were primarily infusion toxicity (grade 1 and 2 f...