A phase I dose-escalation study of XL147 (SAR245408), a PI3K inhibitor administered orally to patients (pts) with advanced malignancies.

3004 Background: XL147 is a selective inhibitor of class I PI3K isoforms. In preclinical cancer models, XL147 is cytostatic or cytoreductive as monotherapy and enhances the efficacy of targeted agents and chemotherapeutics. This open label, phase I dose escalation study assesses the safety, pharmacokinetics, pharmacodynamics and activity of XL147 in pts with advanced solid tumors and lymphoma. Methods: Using a standard 3 + 3 design, pts with solid tumors receive once daily XL147 on days 1-21 (21/7) or as a continuous daily dose (CDD) in 28-day cycles. Cycle 1 safety data determine dose-limiting toxicities (DLTs). Disease assessments occur every 8 weeks. The potential utility of pan-Class I PI3K inhibition in lymphoma pts will be explored. Results: 68 solid tumor pts have been treated: 41 on 21/7, 21 on CDD using capsules, and 6 on CDD using tablets. The MTD for 21/7 and preliminary MTD for CDD was 600 mg; MTD expansion in NSCLC and other solid tumor pts at 600 mg XL147 CDD is ongoing. Drug-related skin ra...