Advanced Cancer: oral MK2461 twice daily and will be treated for 28 day cycles. Patients will be enrolled in cohorts and will be treated at sequentially rising dose levels of MK2461. 60 mg dry filled capsules, escalating to 240 mg

MK-2461 inhibits HGF-induced mitogenesis of 4MBr-5 (monkey lung epithelial cells) with IC50 of 204 nM, and HGF-induced migration of HPAF II ( human pancreatic adenocarcinoma cells) with IC50 of 404 nM, as well as HGF-induced branching tubulogenesis of Madin-Darby canine kidney (MDCK) type II cell lines. In addition, MK-2461 potently inhibits IL-3-independent proliferation of Murine myeloid 32D cells transformed with Tpr-Met or Tpr-Met (Y362C) mutant with IC50 of ~100 nM. MK-2461 significantly inhibits the proliferation of a large panel of tumor cell lines, especially potent against tumor cells harbored genomic amplification of MET or FGFR2. MK-2461 also potently inhibits FGFR1, FGFR2, FGFR3, KDR, TrkA, TrkB, and Flt4. Compared with wild-type c-Met, MK-2461 more potently inhibits the activity of oncogenic c-Met kinase mutants such as N1100Y, Y1230C, Y1230H, Y1235D, and M1250T with IC50 of 1.5 nM, 1.5 nM, 1.0 nM, 0.5 nM, and 0.4 nM, respectively. MK-2461 binds more strongly to phosphorylated c-Met than to unphosphorylated c-Met.