Background: Idelalisib (IDELA), an oral inhibitor of PI3Kδ, is highly active in heavily pretreated patients with CLL as single agent or combined with rituximab (R) as demonstrated in Phase 1 trials. Methods: A Phase 3 study evaluated IDELA+R vs placebo (PBO)+R in pts with CLL requiring therapy after progression <24 mos since completion of last therapy and considered unfit to receive cytotoxic therapy. Primary endpoint PFS was assessed by IRC and standard criteria (Hallek 2008/2012, Cheson 2012). After progression, pts 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 et al, 2014) led to a decision of early stop for overwhelming efficacy. Results: 220 pts (110/group) with median age of 71 yrs (78% ≥65 yrs), median time since diagnosis of 8.5 yrs, and median number of 3 prior therapies (range: 1-12) were randomized. 44% of pts had del17p/TP53 mutation, 84% had unmutated IGHV. Table 1 summarizes efficacy and safety. Conclusions: Similar to the first interim analysis, IDELA+R demonstrated significant improvement in PFS, ORR, and LNR compared to control, with acceptable safety. OS of pts on IDELA+R remains superior, including pts that crossed over into the extension study. Clinical trial information: NCT01539512.

*3/5 pts w/colitis on IDELA+R also reported diarrhea; **Includes 16 preferred terms.