Results From The Phase 3 Duotm 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 (O9Brien, 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 59 th Annual Meeting in December. Methods: Eligible patients must have received at least 1 prior therapy, had an Eastern Cooperative Oncology Group (ECOG) score of 0-2, and a platelet count ≥ 10 G/L at baseline. Patients were randomized 1:1 to either oral DUV 25 mg BID administered until disease progression or IV OFA 300 mg x1 then 2000 mg for 12 doses total, per label. Response assessment occurred on Day 1 of Cycle 3 (C3), C5, C7, C11, C15, C19, and every 6 months thereafter. The primary endpoint was progression-free survival (PFS) as assessed by a blinded independent review committee (IRC). Key secondary endpoints included ORR, overall survival (OS), and safety. Results: Demographics and Baseline Characteristics The DUO study completed enrollment in December 2015. A total of 319 patients were enrolled and randomized at 59 sites, globally. The median age was 69 years (range: 39-90), with 68% of patients ≥ 65 years. Most patients were male (60%) and Caucasian (92%). Key disease characteristics are presented below. Enrolled patients had a median of 2 prior therapies (range: 1-10), while 33% had ≥ 3 prior therapies. Patients had a median of 20 months since their last anticancer therapy (range: 0.5-149), with 36% less than 12 months from their last therapy. Nearly all patients (94%) had received prior alkylator therapy (chlorambucil 36%, bendamustine 38%, cyclophosphamide 65%); most patients (80%) had received prior rituximab; 66% of patients received prior purine analogue therapy. Sixty-one (19.1%) patients were refractory to purine analog therapy, defined as progression within 12 months of completion of fludarabine/pentostatin treatment. Efficacy and Safety The final unblinded efficacy and safety analyses will be presented at the 59 th Annual American Society of Hematology Meeting in December, and include the primary and key secondary endpoints of PFS, ORR, and OS and safety for both treatment arms, including the rates of adverse events (AEs), severe AEs, and AEs leading to treatment discontinuation. Clinical trial information: NCT02004522. Disclosures Flinn: Forty Seven: Research Funding; Calithera: Research Funding; Constellation: Research Funding; TG Therapeutics: Research Funding; Verastem: Research Funding; Merck: Research Funding; Genentech: Research Funding; Novartis: Research Funding; Beigene: Research Funding; KITE: Research Funding; Agios: Research Funding; Acerta: Research Funding; Curis: Research Funding; Janssen: Research Funding; Gilead: Research Funding; Janssen: Research Funding; Seattle Genetics: Research Funding; Pharmacyclics LLC: Research Funding; AbbVie Company: Research Funding; Incyte: Research Funding; Portola: Research Funding; Celgene: Research Funding; Takeda: Research Funding; Trillium: Research Funding; Pfizer: Research Funding; Pharmacyclics: Research Funding; Infinity: Research Funding. Hillmen: GSK: Consultancy, Honoraria, Research Funding; Novartis: Honoraria, Research Funding; Roche: Consultancy, Honoraria, Research Funding; Celgene: Research Funding; Pharmacyclics LLC, an AbbVie Company: Honoraria, Research Funding; Alexion Pharmaceuticals, Inc.: Consultancy, Honoraria; AbbVie: Consultancy, Honoraria, Research Funding; Gilead: Consultancy, Honoraria, Research Funding; Janssen: Consultancy, Honoraria, Research Funding. Montillo: Abbvie: Honoraria, Membership on an entity9s Board of Directors or advisory committees; Novartis: Honoraria; Roche: Honoraria, Research Funding; Gilead: Honoraria, Membership on an entity9s Board of Directors or advisory committees; Janssen: Honoraria, Membership on an entity9s Board of Directors or advisory committees. Etienne: BMS: Speakers Bureau; Incyte: Speakers Bureau; Novartis: Consultancy, Research Funding. Delgado: Abbvie, Jansen, Gilead, Roche: Consultancy, Speakers Bureau. Tam: Roche: Honoraria, Research Funding; Abbvie: Honoraria, Research Funding; Janssen Cilag: Honoraria, Research Funding. Davids: Celgene: Consultancy; Abbvie: Consultancy, Membership on an entity9s Board of Directors or advisory committees, Research Funding; TG Therapeutics: Membership on an entity9s Board of Directors or advisory committees, Research Funding; Janssen: Consultancy, Membership on an entity9s Board of Directors or advisory committees; Merck: Consultancy; Astra-Zeneca: Consultancy; Infinity: Consultancy, Research Funding; InCyte: Membership on an entity9s Board of Directors or advisory committees; Gilead: Membership on an entity9s Board of Directors or advisory committees; Genentech: Consultancy, Membership on an entity9s Board of Directors or advisory committees, Research Funding; Pharmacyclics: Consultancy, Membership on an entity9s Board of Directors or advisory committees, Research Funding. Lamanna: Gilead: Membership on an entity9s Board of Directors or advisory committees, Research Funding. Jaeger: Celgene: Honoraria, Membership on an entity9s Board of Directors or advisory committees; Janssen: Consultancy, Honoraria, Membership on an entity9s Board of Directors or advisory committees, Other: Travel, Accommodations, Expenses; Roche: Consultancy, Honoraria, Membership on an entity9s Board of Directors or advisory committees, Other: Travel, Accommodations, Expenses; Novartis Pharmaceuticals Corporation: Honoraria, Membership on an entity9s Board of Directors or advisory committees, Research Funding. Ghia: Janssen Pharmaceuticals: Honoraria, Research Funding; AbbVie: Consultancy, Honoraria, Membership on an entity9s Board of Directors or advisory committees, Research Funding; Roche: Honoraria; Gilead: Consultancy, Honoraria, Membership on an entity9s Board of Directors or advisory committees, Research Funding, Speakers Bureau. Cymbalista: AbbVie: Consultancy, Honoraria; Janssen: Consultancy, Honoraria, Other: Travel, Accommodations, Expenses, Research Funding; Mundipharma: Honoraria; Gilead: Consultancy, Honoraria; Roche: Other: Travel, Accommodations, Expenses. Portell: Roche/Genentech: Research Funding; Acerta: Research Funding; AbbVie: Research Funding; Infinity: Research Funding; TG-Therapeutics: Research Funding. Skarbnik: Abbvie: Other: Ad board, Speakers Bureau; Genentech: Speakers Bureau; Novartis: Speakers Bureau; Gilead: Speakers Bureau; Seattle Genetics: Speakers Bureau. Cashen: Kite Pharma: Speakers Bureau; Gilead: Speakers Bureau; Celgene: Speakers Bureau; Seattle Genetics: Speakers Bureau. Kelly: Verastem: Employment. Turnbull: Verastem Inc.: Employment. Stilgenbauer: AbbVie: Consultancy, Honoraria, Research Funding; Boehringer-Ingelheim: Consultancy, Honoraria, Research Funding; Mundipharma: Consultancy, Honoraria, Research Funding; Genentech: Consultancy, Honoraria, Research Funding; Amgen: Consultancy, Honoraria, Research Funding; Pharmacyclics: Consultancy, Honoraria, Research Funding; Novartis: Consultancy, Honoraria, Research Funding; Hoffman La-Roche: Consultancy, Honoraria, Research Funding; Genzyme: Consultancy, Honoraria, Research Funding; Celgene: Consultancy, Honoraria, Research Funding; Janssen: Consultancy, Honoraria, Research Funding; Gilead: Consultancy, Honoraria, Research Funding; GSK: Consultancy, Honoraria, Research Funding; Sanofi: Consultancy, Honoraria, Research Funding.