A phase I dose-escalation study of the safety and pharmacokinetics (PK) of XL184, a VEGFR and MET kinase inhibitor, administered orally to patients (pts) with advanced malignancies

14031 Background: XL184 is a potent orally available small molecule inhibitor of MET and VEGFR2/KDR, and also inhibits KIT, RET, FLT3, and Tie-2. Methods: This is a ph 1 cohort dose escalation study. Pts with advanced malignancies are treated with 2 cycles of XL184 orally daily for 5 consecutive days every 2 weeks. Response is assessed every 8 wks by RECIST criteria and pts with SD or better receive maintenance therapy. Plasma markers of angiogenesis VEGF-A, sVEGFR2 and Ang2 are being analyzed. Results: A total of 25 pts with advanced malignancies have been treated across 7 dose levels: 0.08 to 5.12 mg/kg. A total of 10 pts have had SD lasting > 3 months. Three pts with medullary thyroid carcinoma (one of whom had a documented RET mutation) had substantial reductions in plasma calcitonin. Three pts have had stable disease for over 6 months, including 1 pt with carcinoid (20% decrease in liver metastases) and 1 pt with T- cell lymphoma (on treatment for >12 mos). One pt with papillary renal cell cancer, a ...