#677 Preliminary Safety and Efficacy Of IPI-145, a Potent Inhibitor Of Phosphoinositide-3-Kinase-δ,γ, In Patients With Chronic Lymphocytic Leukemia
Program: Oral and Poster Abstracts
Session: 642. CLL: Therapy, excluding Transplantation: Clinical Trials of B Cell Receptor Signaling Inhibitors
Monday, December 9, 2013: 5:30 PM
295-296 (Ernest N. Morial Convention Center)
Ian Flinn, MD, PhD1, Manish Patel, MD1,2*, Brad S. Kahl, MD3, Steven M. Horwitz, MD4, Francine M. Foss, MD5, Yasuhiro Oki, MD6, Pierluigi Porcu, MD7, Jennifer Sweeney, BS8*, Kerstin Allen, MA8*, Kerrie Faia, MS8*, Patricia Harris, MPH8*, Joi Dunbar, PharmD8*, Howard M. Stern, M.D., Ph.D.8*, Patrick Kelly, MD8 and Susan O’Brien, MD6
Clinical activity has been observed in R/R CLL pts at all doses of IPI-145 studied from 8 mg to 75 mg BID and in pts with R/R high-risk disease (TP53 mut/17pdel). Treatment-related lymphocytosis is rapid, with the median ALC return to baseline within 6 cycles of treatment. Reduction in adenopathy occurs early with no apparent dose-dependence. Nodal responses (>50% reduction in adenopathy by CT assessment) occurred in 79% of pts after 2 treatment cycles. Best overall response (based on investigator assessment per IWCLL) in evaluable pts to date (median [range] number of cycles 5.1 [1-21.1]) is 52%, with 1 CR, 15 PR, 14 SD and 1 PD. The ORR for the 19 evaluable pts treated at ≤25 mg BID is 53% (10/19; including 1 CR) and 7 of the 8 SD pts achieving nodal response. Resolution of lymphocytosis may lead to an increase in best ORR for SD pts who remain on study. R/R pts with high-risk disease (TP53 mut/17pdel) had similar ORR.
Conclusions: IPI-145, an oral, potent PI3K-δ,γ inhibitor, appears well tolerated and has shown promising clinical activity in pts with R/R CLL across the range of doses examined. The PK/PD and clinical activity suggest that 25 mg BID is a biologically active dose in R/R CLL, and this dose has been selected for an upcoming randomized Phase 3 trial in R/R CLL. Updated data from treatment-naïve CLL pts who received IPI-145 at 25 mg BID and R/R CLL pts who received IPI-145 at 25 mg and 75 mg BID will be presented.