Background: The phosphatidylinositol 3-kinase (PI3K) pathway is a promising target in cancer. CH5132799 is a novel PI3K inhibitor, selectively inhibiting class I PI3Ks (α, β, δ and γ) with no inhibition of class II and III or mTOR, and with potent antitumor activity in preclinical studies (Tanaka et al, Clin Cancer Res; 17; 3272-81, 2011). First-in-human study objectives were determination of maximum tolerated dose (MTD), safety/tolerability, PK/PD and clinical activity (RECIST). Methods: A 3+3 dose escalation design was used. The initial dosing schedule of CH5132799(schedule A) was once a day (QD). Due to a relatively short half-life, a twice a day (BID) schedule (schedule B) was introduced. PK profiles were studied over 72 hours. PD analyses included quantification of various phosphoproteins in platelet rich plasma (PRP). Tumor assessments were performed at baseline and cycle 3 day 1 (C3D1) and FDG-PET scans at baseline, C1D8 and C3D1. Results: 29 patients (pts) with a variety of solid tumors have been treated (A 23 pts, B 6 pts, the most common tumors were breast, oesophageal, colorectal and ovarian). The starting doses were 2 mg (A) and 48 mg (B). The current doses being explored are 96 mg (A) and 72 mg (B). The most frequently reported drug-related AEs were Grade 1/2 diarrhea, nausea, fatigue, anorexia and anemia. 1 DLT (Grade 3 elevated LFT) was observed in a hepatocellular carcinoma pt at 48 mg BID. MTD has not yet been determined. The preliminary mean ±SD C_max and AUC at 96 mg QD were 202±129 ng/ml and 1407±935 ng·hr/ml respectively, which is consistent with an efficacious exposure based on preclinical models. Some patients achieved the expected exposure at over 32 mg. From single dose of 48mg there was a reduction of phosphorylation of AKT in PRP after treatment, consistent with pathway modulation. A patient with clear cell ovarian cancer and a PIK3CA mutation treated at 48 mg BID showed >50% decrease in SUV on a PET scan at C1D8 and a 75% decrease in CA-125 at C2D1. 5 pts exhibited SD (>8 weeks). Conclusions: CH5132799 is well tolerated either QD ≤96 mg or BID ≤48 mg. Dose-escalation continues and updated safety/efficacy/PK/PD data will be presented.