Second Interim Analysis of a Phase 3 Study Evaluating Idelalisib and Rituximab for Relapsed Chronic Lymphocytic Leukemia

302 Second Interim Analysis of a Phase 3 Study Evaluating Idelalisib and Rituximab for Relapsed Chronic Lymphocytic Leukemia John M. Pagel, Steven E. Coutre, Richard R. Furman, Jeff P. Sharman, Bruce D. Cheson, Peter Hillmen, Jacqueline C. Barrientos, Andrew D. Zelenetz, Thomas J. Kipps, Ian W. Flinn, Ghia Paolo, Herbert A. Eradat, Thomas Ervin, Nicole Lamanna, Bertrand Coiffier, Andrew Pettitt, Xiaoming Li, Thomas M. Jahn, Susan M. O’Brien, Michael J. Hallek 1Fred Hutchinson Cancer Research Center, Seattle, United States, 2Stanford Cancer Center, Stanford, 3Weill Cornell Medical College, New York, 4Willamette Valley Cancer Institute and Research Center/US Oncology Research, Springfield, 5Georgetown University Medical Center, Washington, 6The Leeds Teaching Hospitals, St. James Institute of Oncology, Leeds, United Kingdom, 7Hofstra North Shore-LIJ School of Medicine, Hampstead, 8Memorial Sloan Kettering Cancer Center, New York, 9University of California School of Medicine, San Diego, 10Sarah Cannon Research Institute, Nashville, 11David Geffen School of Medicine at University of California, Los Angeles, Los Angeles, 12Columbia University Medical Center, New York, United States, 13Lyon Sud University Hospital, Pierre-Benite, France, 14University of Liverpool, Liverpool, United Kingdom, 15Gilead Sciences, Foster City, 16Gilead Sciences, Foster City 17University of Texas MD Anderson Cancer Center, Houston, United States, 18University of Cologne, Cologne, Germany Introduction: Idelalisib (IDELA), an oral inhibitor of PI3Kδ, is highly active in heavily pretreated patients with CLL as a single agent or combined with rituximab (R) as demonstrated in Phase 1 trials. Objectives: This report presents the results from the second interim analysis of a Phase 3, randomized, double-blind, placebo-controlled study of IDELA+R vs. placebo (PBO)+R. Methods: Patients with CLL requiring therapy after progression <24 mos since completion of last therapy and considered unfit to receive cytotoxic therapy were enrolled. Primary endpoint PFS was assessed by IRC and standard criteria (Hallek 2008, Hallek 2012, Cheson 2012). After progression, patients could enroll into a blinded extension study to receive IDELA at 150 mg BID (prior PBO+R) or 300 mg BID (prior IDELA+R). The first interim analysis (Furman, NEJM 2014) led to the decision of early termination due to overwhelming efficacy. Results: A total of 220 patients (110 patients on each arm) with a median age of 71 yrs (78% ≥65 yrs), a median time since diagnosis of 8.5 yrs, and a median number of 3 prior therapies (range: 1-12) were randomized. 44% of patients had del(17p)/TP53 mutation, 84% had unmutated IGHV. The table summarizes efficacy and safety. Conclusion: Similar to the first interim analysis, IDELA+R demonstrated significant improvement in progression-free survival, overall response rate, and lymph node response rate, compared to control, with acceptable safety. The overall survival of patients on IDELA+R remained superior, including patients that crossed over into the extension study. Disclosure of Interest: J. Pagel Grant / Research Support from: Gilead Sciences, S. Coutre Grant / Research Support from: Gilead Sciences, R. Furman Grant / Research Support from: Gilead Sciences, J. Sharman Grant / Research Support from: Gilead Sciences, B. Cheson Grant / Research Support from: Gilead Sciences, P. Hillmen Grant / Research Support from: Gilead Sciences, J. Barrientos Grant / Research Support from: Gilead Sciences, A. Zelenetz Grant / Research Support from: Gilead Sciences, T. Kipps Grant / Research Support from: Gilead Sciences, I. Flinn Grant / Research Support from: Gilead Sciences, H. Eradat Grant / Research Support from: Gilead Sciences, N. Lamanna Grant / Research Support from: Gilead Sciences, B. Coiffier Grant / Research Support from: Gilead Sciences, A. Pettitt Grant / Research Support from: Gilead Sciences, X. Li Shareholder of: Gilead Sciences, Employee of: Gilead Sciences, T. Jahn Shareholder of: Gilead Sciences, Employee of: Gilead Sciences, S. O’Brien Grant / Research Support from: Gilead Sciences, M. Hallek Grant / Research Support from: Gilead Sciences