Background: Aurora kinases A, B, and, C play essential roles in regulating cell division. Overexpression of aurora A and B in human tumors is associated with high proliferation rates and poor prognosis. AMG 900 is an investigational, orally administered, highly selective inhibitor of aurora A, B, and C that demonstrated activity in drug-resistant cell lines and human tumor xenografts. This study evaluated the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics of AMG 900. Methods: Key eligibility criteria: ≥ 18 years old, advanced solid tumors, measurable disease, ECOG ≤ 2, and adequate organ function. AMG 900 was administered orally daily for 4 consecutive days (D) every 2 weeks (Q2W). In the dose-escalation phase, the starting dose was 1 mg and was escalated by 100% in subsequent cohorts (1 pt/cohort) until dose limiting toxicity (DLT) or grade 2 (G2) AMG 900-related toxicity occurred in the first 28 D. Dose escalation continued in a standard 3+3 design at ≤ 25% if DLT occurred or ≤ 50% if G2 related toxicity occurred. The maximum tolerated dose (MTD) was determined without prophylactic G-CSF support. Results: As of OCT 2011, 19 pts (1 pt at 1, 2, 4, and 8 mg; 3 pts at 16 mg; and 6 pts at 24 and 30 mg) had received ≥ 1 dose of AMG 900. Demographics were 58% women, median age 60 (32-77) years, and ECOG 0/1, 63%/37%. There were 4 DLTs: G4 neutropenia > 7 days at 24 mg (n=1) and 30 mg (n=1); G4 neutropenia > 7 days + G4 thrombocytopenia at 30 mg (n=1); and febrile neutropenia (FN) at 30 mg (n=1). MTD without G-CSF support was 24 mg. 89% of pts had treatment-related adverse events (AEs). G≥3 treatment-related AEs were neutropenia, 8 (42%); leukopenia, 4 (21%); anemia, 2 (11%); thrombocytopenia, 1 (5%); and FN, 1 (5%). Preliminary PK showed no obvious departures from dose-proportionality with a half-life of ~16 h. Tumor-response data were available for 17 pts: stable disease, 13 pts (range 0.4 to 43.7 wks); progressive disease, 4 pts. One pt (16 mg cohort) with recurrent ovarian cancer had 16% tumor shrinkage and 45% decrease in CA-125 (SD > 6 months). Conclusions: AMG 900 administered at 24 mg daily for 4D Q2W is the recommended dose for phase 2 trials. Dose escalation is now ongoing to determine the MTD with prophylactic G-CSF.