The pharmacodynamic effect of TKI258 on plasma biomarkers of angiogenesis in patients with AML and advanced melanoma

14680 Background: TKI258 (dovitinib lactate), is a multi-tyrosine kinase inhibitor of VEGF receptors-1,2,3, FGF receptors-1, 2, 3, PDGFR-β, c-KIT and FLT3. To evaluate the pharmacodynamic effect of TKI258 in patients, a panel of plasma angiogenesis biomarkers were evaluated in two Phase I clinical trials - acute myeloid leukemia (AML) and locally advanced or metastatic melanoma. Methods: Plasma samples were analyzed from selected dosing groups of patients during the dose escalation stages of the two Phase I trials. 19 AML patients received TKI258 at doses ranging 200 - 600 mg/day, with an initial 14 day cycle (7 days on/7 days off), followed by a continuous daily dosing schedule (28 day cycle). 16 melanoma patients received 200 - 500 mg/day on once daily dosing (28 day cycle). Plasma VEGF, placental growth factor (PLGF), basic FGF (bFGF), and soluble VEGFR1 and VEGFR2 (sVEGFR1 and 2) were measured by multiplex assays using Meso-Scale Discovery platform. Plasma levels of each marker were frequently monitor...