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Blood. 2018 Dec 6;132(23):2446-2455. doi: 10.1182/blood-2018-05-850461. Epub 2018 Oct 4.

The phase 3 DUO trial: duvelisib vs ofatumumab in relapsed and refractory CLL/SLL.

Author information

1
Sarah Cannon Research Institute, Nashville, TN.
2
Tennessee Oncology, Nashville, TN.
3
St. James's Institute of Oncology, The Leeds Teaching Hospitals, Leeds, United Kingdom.
4
Department of Haematology and Oncology, Niguarda Cancer Center, Niguarda Hospital, Milan, Italy.
5
First Department of Internal Medicine, Semmelweis University, Budapest, Hungary.
6
Department of Hematology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary.
7
Hematology Department, Institut Bergonie, Bordeaux, France.
8
Hospital Clinic, Barcelona, Spain.
9
Flinders Medical Centre-Flinders University, Bedford Park, SA, Australia.
10
Peter MacCallum Cancer Centre, St. Vincent's Hospital and University of Melbourne, Melbourne, VIC, Australia.
11
Department of Internal Medicine and Hematology, Petz Aladár County Hospital, Győr, Hungary.
12
Hematology, University Hospital Ghent, Gent, Belgium.
13
Florida Cancer Specialists, Venice, FL.
14
Department of Hematology, University Hospital Vall d'Hebron, Barcelona, Spain.
15
Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA.
16
New York Presbyterian, Columbia University Medical Center, New York, NY.
17
Division of Hematology and Hemostaseology, Department of Medicine I, Medical University of Vienna, Vienna, Austria.
18
Universita' Vita-Salute San Raffaele and San Raffaele Scientific Institute, Milan, Italy.
19
Laboratoire d'hématologie, Hôpital Avicenne, Paris, France.
20
Division of Hematology and Oncology, University of Virginia, Charlottesville, VA.
21
John Theurer Cancer Center, Hackensack Meridian Health, Hackensack, NJ.
22
Siteman Comprehensive Cancer Center, Washington University, St. Louis, MO.
23
Verastem Oncology, Needham, MA.
24
Department III of Internal Medicine, University Hospital Ulm, Ulm, Germany; and.
25
Klinik für Innere Medizin I, Universitätsklinikum des Saarlandes, Homburg, Germany.

Abstract

Duvelisib (also known as IPI-145) is an oral, dual inhibitor of phosphatidylinositol 3-kinase δ and γ (PI3K-δ,γ) being developed for treatment of hematologic malignancies. PI3K-δ,γ signaling can promote B-cell proliferation and survival in clonal B-cell malignancies, such as chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL). In a phase 1 study, duvelisib showed clinically meaningful activity and acceptable safety in CLL/SLL patients. We report here the results of DUO, a global phase 3 randomized study of duvelisib vs ofatumumab monotherapy for patients with relapsed or refractory (RR) CLL/SLL. Patients were randomized 1:1 to oral duvelisib 25 mg twice daily (n = 160) or ofatumumab IV (n = 159). The study met the primary study end point by significantly improving progression-free survival per independent review committee assessment compared with ofatumumab for all patients (median, 13.3 months vs 9.9 months; hazard ratio [HR] = 0.52; P < .0001), including those with high-risk chromosome 17p13.1 deletions [del(17p)] and/or TP53 mutations (HR = 0.40; P = .0002). The overall response rate was significantly higher with duvelisib (74% vs 45%; P < .0001) regardless of del(17p) status. The most common adverse events were diarrhea, neutropenia, pyrexia, nausea, anemia, and cough on the duvelisib arm, and neutropenia and infusion reactions on the ofatumumab arm. The DUO trial data support duvelisib as a potentially effective treatment option for patients with RR CLL/SLL. This trial was registered at www.clinicaltrials.gov as #NCT02004522.

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