A phase III, randomized, double-blind, placebo-controlled study evaluating the efficacy and safety of idelalisib (GS-1101) in combination with rituximab for previously treated indolent non-Hodgkin lymphomas (iNHL)

TPS8617 Background: PI3K-delta is critical for activation, proliferation and survival of B cells and plays a role in homing and retention in lymphoid tissues. PI3Kδ signaling is hyperactive in many B-cell malignancies. Idelalisib is a first-in-class, targeted, highly selective, oral inhibitor of PI3Kδ that reduces proliferation, enhances apoptosis, and inhibits homing and retention of malignant B cells in lymphoid tissues (Lannutti et al, 2011). Phase 1 trials demonstrated that idelalisib is highly active in pts with heavily pretreated iNHL: pts experienced reductions in disease-associated chemokines, profound and rapid reductions in lymphadenopathy, and durable clinical benefit with acceptable safety profile (de Vos et al, 2011). Methods: 375 pts with previously treated iNHL, who have measurable lymphadenopathy, have received prior anti-CD20-antibody-containing therapy, and who have iNHL that is not refractory to rituximab (R) are randomized in a 2:1 ratio into Arm A or Arm B. In Arm A, pts receive idelalisib at 150 mg BID continuously + R at 375 mg/m2 (weekly x 4 then every 8 weeks x 4). In Arm B, pts receive placebo BID instead of idelalisib. Stratification factors include tumor type (follicular lymphoma vs others), tumor burden (high vs low), and time since completion of last prior therapy for iNHL (