Background: Patients (pts) with metastatic endometrial carcinoma have a poor prognosis and PIK3CA mutations and amplifications are common in these cancers. This study evaluated the efficacy and safety of a pure PI3K inhibitor BKM120 in advanced or recurrent endometrial carcinoma. Methods: This multicenter, single-arm, Phase II, double strata (histological low grade (LG) vs. high grade (HG)) open-label study enrolled pts with histologically confirmed advanced or recurrent endometrial carcinoma, who had received no more than one prior chemotherapy regimen. Primary endpoints were proportion of pts with progression-free survival (PFS) at 2 months (HG strata) or at 3 months (LG strata), objective response rate (ORR), and safety. Initial BKM120 dosage was 100 mg tablets once daily. Results: 40 pts were enrolled, of which 16 pts had received BKM120 at 100 mg/d. Due to high rate of grade 3/4 toxicities (cutaneous rash (54%), depressive events (47%), and anxiety (40%)), the IDMC proposed to stop recruitment at 100 mg but to continue the recruitment with a lower dose of 60 mg/d. 24 pts (median age 67 years old) were newly enrolled (14 in the LG strata, 10 in the HG strata). Rate of PFS > 2months in the HG strata was 70% and > 3months was 57% in the LG strata. Median PFS for all pts is 4.5 months (CI 95% 2.8 – 6.1); median PFS for LG strata is 8.3 months compared to 3.8 months for the HG strata. No objective response was reported. At 60 mg/d, 87% of patients experienced grade 3/4 toxicity. The most commonly reported treatment-related grade ≥ 3 AEs were cutaneous (13%), increased alanine aminotransferase (13%), HTA (17%), hyperglycemia (17%) and increased aspartate aminotransferase (21%). 5 patients (21%) stopped BKM120 for toxicity. Conclusions: BKM120 was associated with an unfavorable safety profile and minimal antitumor activity in monotherapy in advanced or recurrent endometrial carcinoma. The clinical trial was stopped before end of recruitment for toxicity. Clinical trial information: NCT01397877