Preliminary Safety And Efficacy Of Ipi-145, A Potent Inhibitor Of Phosphoinositide-3-Kinase-Delta,Gamma, In Patients With Relapsed/Refractory Cll.

7070 Background: Phosphoinositide-3-kinases (PI3Ks) are pivotal in cell signaling and regulate a variety of cellular functions relevant to oncogenesis. IPI-145, a potent oral inhibitor of the PI3KEδ and PI3K-γ isoforms, is in clinical development for patients (pts) with hematologic malignancies. Early results in pts with relapsed/refractory chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL) from an ongoing Phase I study are reported here. Methods: This dose-escalation study evaluates the safety, maximum tolerated dose (MTD), clinical activity, and pharmacokinetics (PK) of IPI-145. Expansion cohorts (EC) u003c MTD are allowed. IPI-145 is given orally twice daily (BID) in 28-day cycles. Tumor response is based on modified IWCLL guidelines criteria. Results: 55 pts have been dosed with IPI-145. PK, available through 50 mg BID, are linear with continuous 24 hr inhibition of pAKT (Ser473) in primary pt CLL cells after a single dose of 25 mg. In the 16 pts with CLL (5 pts in dose escalation u003c 25 mg BID a...