Antitumor efficacy of OSI-930 and the molecular targeted agent erlotinib in preclinical xenograft models

14596 Background: OSI-930 is a potent Kit/KDR inhibitor that is currently in Phase I clinical trials. Preclinically OSI-930 has demonstrated significant anti-tumor activity as a monotherapy in a variety of tumor xenograft models. We have previously shown that OSI-930 can be administered safely and effectively with standard-of-care chemotherapeutics in xenograft models of both small cell lung cancer as well as colorectal carcinoma (Srebernak, et al., AACR 2005). In order to further our understanding of the potential clinical utility of OSI-930 we sought to investigate the combination of OSI-930 with erlotinib, a small molecule tyrosine kinase inhibitor of the epidermal growth factor receptor (EGFR) in a preclinical setting. Emerging clinical data suggest that continuation of erlotinib treatment in patients with progressive disease may be beneficial even when a new treatment is initiated. Thus, we investigated whether this phenomenon could be reproduced in a preclinical setting and whether combining OSI-930...