Oral PI3 kinase inhibitor BKM120 monotherapy in patients (pts) with advanced solid tumors: An update on safety and efficacy.

3043 Background: PI3K pathway is frequently altered in cancer and can have an impact on tumor survival and proliferation. BKM120 is a potent and highly specific oral pan-class I PI3K inhibitor without mTOR and Vps34 activity. Methods: Phase I dose-escalation (DE) study followed by an expansion cohort of daily BKM120 in pts with advanced solid tumors. Bayesian logistic regression model with overdose control guided the DE. Pts in the MTD expansion arm were pre-selected for molecular alterations of PI3K and/or PTEN. Results: 77 pts received oral BKM120 once daily thus far; data on 66 pts, median age 55 y (30-77), are reported here. 6 dose levels were explored: 12.5 mg (1 pt); 25 mg (2 pts), 50 mg (5 pts), 80 mg (11 pts), 100 mg (43 pts), 150 mg (4 pts). Most common tumor types: CRC (24 pts), breast cancer (BC) (18 pts), lung (3 pts) and endometrial (3 pts) cancer. Median duration of treatment was 7.5 wks (0.1-69+) with 18 pts treated for >16 wks. Seven dose-limiting toxicities (DLTs) were observed: 2x G4 hyp...