Safety and activity of the chemotherapy-free triplet of ublituximab, TGR-1202, and ibrutinib in relapsed B-cell malignancies.

8501 Background: Multiple novel targeted agents are emerging for B-cell malignancies, but few studies have successfully and safely combined these agents. Ublituximab (UTX) is a novel glycoengineered mAb targeting a unique epitope on the CD20 antigen. TGR-1202 is a next generation, once daily, PI3Kδ inhibitor, active in patients (pts) with rel/ref hematologic malignancies (Burris, 2014). This Ph 1 trial evaluates the safety of the first triplet combination of a novel anti-CD20 + PI3Kδ + BTK inhibitor in pts with B-cell malignancies. Methods: Eligible pts had rel/ref CLL (including Richter’s) or B-cell NHL with an ECOG PS ≤ 2 w/o limit to number of prior therapies. Pts refractory to prior PI3Kδ or BTK were eligible. CLL & NHL cohorts were evaluated independently in a 3+3 dose escalation design to evaluate safety and dose limiting toxicities (DLT). UTX was dosed at 900mg on D 1, 8, 15 of Cyc 1 & 2 and D 1 on Cyc 4, 6, 9 & 12. TGR-1202 was dose escalated (400mg, 600mg, 800mg, 1200mg). Ibrutinib was dosed at 4...