Phase lb study of buparlisib (BKM120) plus either paclitaxel (PTX) in advanced solid tumors (aST) or PTX plus trastuzumab (TZ) in HER2+ breast cancer (BC).

627^ Background: Preclinical data show PI3K-pathway inhibition can enhance the efficacy of anticancer therapy, such as PTX or TZ. In this 4-arm Ph Ib study (NCT01285466), buparlisib (pan-PI3K inhibitor) or BEZ235 (dual PI3K/mTOR inhibitor) was combined with PTX in pts with aST or PTX + TZ in pts with HER2+ BC. Here we report the buparlisib arms only. Methods: Pts with aST or HER2+ BC eligible for PTX ± TZ received oral buparlisib qd + PTX (70−80 mg/m2 IV) qw ± TZ (2 mg/kg IV) qw in 28-day cycles. The primary objective was to define the MTD in each arm by assessing dose-limiting toxicities (DLT) in Cycle (C) 1. Dose escalation was guided by a Bayesian logistic regression model with overdose control. Pts with PI3K-pathway alterations were enrolled in a buparlisib + PTX safety expansion cohort. Results: (2 Apr 2013) Buparlisib + PTX: buparlisib doses from 40−120 mg/d were tested in 53 pts, including 36 pts at 100 mg/d. Median no. prior regimens was 3 (1−12). DLT occurred in 5 pts: 3 at 120 mg and 2 at 100 mg...