Results from the Phase 3 DUO™ Trial: A Randomized Comparison of Duvelisib Vs Ofatumumab in Patients with Relapsed/Refractory Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma

Background: Despite the recent development of novel targeted therapies to treat chronic lymphocytic leukemia or small lymphocytic lymphoma (CLL/SLL), the disease remains incurable and many patients will eventually relapse despite optimal treatment. Additional therapies targeting novel pathways are needed for patients with relapsed/refractory CLL/SLL. Duvelisib (DUV) is an oral dual inhibitor of PI3K-δ and PI3K-γ being developed for the treatment of advanced B-cell malignancies, including CLL/SLL. In a Phase 1 study, the overall response rate (ORR) for DUV monotherapy in relapsed/refractory CLL/SLL (n=55) was 56% (with 1 complete response [CR]) per International Workshop on Chronic Lymphocytic Leukemia (iwCLL) criteria. Based on the safety and efficacy findings in this study, DUV 25 mg twice daily (BID) was selected as the recommended Phase 2 dose (RP2D) in CLL/SLL (O'Brien, ASH 2015). Herein we report the blinded baseline characteristics and disease history from DUO™, a Phase 3 randomized study evaluating DUV monotherapy vs ofatumumab (OFA) monotherapy in patients with relapsed or refractory CLL/SLL. The DUO study completed enrollment in December 2015 and the protocol-defined final analysis (185 progression-free survival [PFS] events) is in progress; the complete trial results will be presented at the American Society of Hematology 59thAnnual Meeting in December.