Background: IDELA (Zydelig) is a selective oral PI3Kδ inhibitor approved in combination with rituximab for previously treated pts with CLL. This open-label study (NCT01659021) compared IDELA + OFA v OFA in pts with relapsed CLL. Methods: Pts with CLL progressing ≤ 24 mo from last therapy, who had received ≥ 2 cycles of a purine analogue or bendamustine, were randomized 2:1 to either Arm A (IDELA 150 mg BID continuously plus OFA, 300 mg IV wk 1, then 1 gm IV wkly x 7 and q 4 wk x 4) or Arm B (OFA, same as Arm A except 2 gm was substituted for 1 gm dosing). Stratification was performed for relapsed v refractory, del17p and/or TP53 mutation, and IGHV mutation. IRC-assessed response and PD based on imaging using modified IWCLL 2008 criteria. The 1^° endpoint was PFS and 2^° endpoints were confirmed ORR, lymph node response (LNR), OS, PFS in pts with del(17p) and/or TP53 mutation, and CR rate. Results are from the final analysis. Results: Pt attributes were balanced in the 2 arms: Med age 67; Rai II/III/IV 18/13/51%, med no. prior regimens 3, refractory 49%, del17p/TP53mut 40%, IGHVunmut 78%. Exposure, disposition, and efficacy are shown in Table. Results were consistent across risk groups. Gr ≥ 3 AEs in Arm A included diarrhea/colitis (20.2%), pneumonia (12.7%), and febrile neutropenia (11.6%). Conclusion: IDELA + OFA yielded superior PFS, ORR, and LNR compared to OFA in relapsed CLL, including within high-risk subgroups. Safety was manageable with a profile similar to that previously observed in CLL trials. The open label design may have led to an imbalance in dropout, with a higher rate in Arm B. Clinical trial information: NCT01659021

¹IDELA med exposure 12.3 mo (0.2-23.9); ²odds ratio; ³per MD; ⁴null hypothesis formally rejected.