FGFRs x PDGFR x c-Kit x FLT3 x VEGFR x AXL

Cancer is a worldwide clinical and economic problem. Conventional approaches to treating cancer include surgery, radiotherapy, and cytotoxic chemotherapy as single modalities or as combined therapies. Recently, targeted therapies including antibodies and small molecule inhibitors have also demonstrated clinical benefit. It is now possible to study different genetic lesions involved in cancer types due to advances in genomic methodologies. The investigational drug in this study, XL999 inhibits multiple receptor tyrosine kinases, including VEGF receptor (VEGFR2/KDR), platelet derived growth factor receptors (PDGFRβ), fms-like tyrosine kinase receptor 3 (FLT3), fibroblast growth factor receptors (FGFR1, FGFR3), RET, and KIT, and thus, interferes with multiple cellular processes simultaneously and will likely have effects on the integrity of tumor neovasculature and angiogenesis. Together with the ability to induce a novel cell cycle arrest, the spectrum of activities that XL999 exhibits may reduce both tumor cell proliferation and angiogenesis in the clinic.
The rationale and purpose of this maintenance study is to allow a subject receiving clinical benefit from XL999 to continue treatment.

The primary objective of this study is to allow rollover of the two remaining subjects from the other XL999 studies to continue to receive XL999.
The secondary objectives of this study are as follows:
To evaluate tumor response after long term repeat administration of XL999 in two subjects rolled over from other XL999 studies.
To characterize the long term safety and tolerability of XL999 after repeat administration in two subjects rolled over from other XL999 studies.
To characterize the long term effects of XL999 on cardiac function after repeat administration in two subjects rolled over from other XL999 studies.

The purpose of this study is to determine the safest dose of XL999 and how well subjects with Non-Small-Cell Lung Cancer tolerate XL999. XL999 is a small molecule inhibitor of multiple kinases including VEGFR, PDGFR, FGFR, FLT-3, and Src, which are involved in tumor cell growth, formation of new blood vessels (angiogenesis), and metastasis.