Results of a phase III randomized, controlled study evaluating the efficacy and safety of idelalisib (IDELA) in combination with ofatumumab (OFA) for previously treated chronic lymphocytic leukemia (CLL).

7023 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%, IGHV unmut 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. Arm A (IDELA/OFA) Arm B (OFA) HR / OR2 Pts randomized/dosed 174/173 87/86 Months on study (range) 13.6 (1.1-24)1 5.8 (0-20) Reason for study D/C3 (%) PD 34 (19.5) 41 (47.1) Death 22 (12.6) 6 (6.9) AE / MD decision 21 (12) 19 (21.8) Withdrew consent/other 13 (7.5) 15 (17.2) Med PFS, mo 16.3 8.0 HR = 0.27, p < 0.00014 ORR, % 75.3 18.4 OR = 15.9, p < 0.00014 LNR, % 93.3 4.9 OR = 487, p < 0.00014 Med OS, mo 20.9 19.4 HR = 0.74, p = 0.27 Med PFS: del17p/TP53mut, mo 13.7 5.8 HR = 0.33, p < 0.0001 1IDELA med exposure 12.3 mo (0.2-23.9); 2odds ratio; 3per MD; 4null hypothesis formally rejected.