Background Phosphatidylinositol 3-kinase (PI3K) is critical to cancer cell growth, survival, and metabolism. BKM120 is an oral pan-class I (α, β, γ, δ) PI3K inhibitor that has demonstrated in vitro and in vivo tumor cell growth inhibition in a range of cancer types including breast cancer. Materials and methods: The Phase I study CBKM120X2101 investigating single-agent daily BKM120 in patients (pts) with advanced solid tumors has been recently completed with the maximum tolerated dose established at 100 mg/day. Here, we report the analysis of metastatic breast carcinoma (MBC) pts enrolled in this study. Results: Overall, 83 pts have enrolled, 21 of whom have MBC. At the cut-off date of 25th February 2011, 20 MBC pts were evaluable: 1 pt at 80 mg, 1 pt at 150 mg and 18 pts at 100 mg. Patient characteristics were as follows: median age 55 years (range 37–71); performance status ECOG 0/1/2 for 7/12/1 pts, respectively; visceral disease was reported in 16 pts, including liver, 10 pts (50%); lung, 9 pts (45%); and pleura, 5 pts (25%); all pts had >3 lines of systemic therapy (3-12). The median time from last treatment and study entry was 46 days (29-235). The median duration of BKM120 treatment administered was 7.5 weeks (1.0−96.4). The most frequent grade 3 drug-related adverse events (AEs) were: transaminases increase, 4 pts; psychiatric disorders, 3 pts, consisting of anxiety, affective disorder, and mood alteration (1 pt each); diarrhea, 2 pts; fatigue, 2 pts; and hyperglycemia, 1 pt. The only grade 4 drug-related AE was hyperglycemia, reported in 1 pt at 150 mg. Most AEs were manageable with treatment interruption and dose reductions. Eighteen pts were evaluable for objective tumor response by RECIST. Two pts (11%) exhibited partial responses, which were confirmed in a triple-negative MBC pt, and unconfirmed in an ER+ HER2− MBC pt. For these 2 pts, the treatment duration was 29+ (ongoing) and 6 months, respectively. An additional 9 pts (50%) had stable disease, lasting >4 months in 7 pts (35%). Conclusions: This preliminary analysis showed that BKM120 has single-agent activity in heavily pretreated pts with MBC, and an acceptable safety profile. Molecular profiling and updated pharmacokinetic results will be presented at the meeting. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P3-16-01.