Deborah A. Smith, Joyce M Antal, L.L. Siu, Philippe L. Bedard, J. L. Gauvin, R. Kurzrock, Laurel M. Adams, T. Gonzalez, H. A. Burris, J. R. Infante, Joanna Opalinska, Kathleen N. Moore, Jennifer J. Wheler, Carla Kurkjian, Shannon R. Morris, Carol Aghajanian, and J. F. Gerecitano
3003 Background: GSK795 is a potent pan-isoform inhibitor of AKT. The objectives were to define the maximum tolerated dose (MTD), and to evaluate the PK, PD and clinical activity of GSK795 in patients (pts) with advanced solid tumors. Methods: GSK795 was given orally, once daily (QD) in this two-part study of dose-escalation (Part 1) with expansion (Part 2) at the MTD in selected tumor types to evaluate the clinical activity. Alternative dosing schedules were also investigated. Results: Preliminary data are available for 66 pts that received ≥ 1 dose of GSK795, including pts with endometrial (12) and prostate cancer (9) as well as other tumor types selected for either PTEN loss or PIK3CA mutation (7). Doses explored were 10, 20, 40, 75, 100 and 150mg QD. The MTD was 75 mg QD. Dose-limiting toxicities were G3 hyperglycemia (n=2), G4 hypoglycemia (n=1), G3 hypoglycemia (n=1), and G2 stomatitis (n=1); all were reversible. The most common (>10%) drug-related adverse events were diarrhea (47%; G3/4 0%), nausea...