The phase 3 DUO trial

Duvelisib vs ofatumumab in relapsed and refractory CLL/SLL

Ian W. Flinn, Peter Hillmen, Marco Montillo, Zsolt Nagy, A. Illés, Gabriel Etienne, Julio Delgado, Bryone J. Kuss, Constantine S. Tam, Zoltán Gasztonyi, Fritz Offner, Scott Lunin, Francesco Bosch, Matthew S. Davids, Nicole Lamanna, Ulrich Jaeger, Paolo Ghia, Florence Cymbalista, Craig A. Portell, Alan P. Skarbnik & 5 others Amanda F. Cashen, David T. Weaver, Virginia M. Kelly, Barry Turnbull, Stephan Stilgenbauer

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

Duvelisib (also known as IPI-145) is an oral, dual inhibitor of phosphatidylinositol 3-kinase d and g (PI3K-d,g) being developed for treatment of hematologic malignancies. PI3K-d,g 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 5 160) or ofatumumab IV (n 5 159). 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] 5 0.52; P < .0001), including those with high-risk chromosome 17p13.1 deletions [del(17p)] and/or TP53 mutations (HR 5 0.40; P 5 .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.

Original languageEnglish
Pages (from-to)2446-2455
Number of pages10
JournalBlood
Volume132
Issue number23
DOIs
Publication statusPublished - Dec 6 2018

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B-Cell Chronic Lymphocytic Leukemia
Refractory materials
Phosphatidylinositol 3-Kinase
Neutropenia
Hazards
B-Lymphocytes
Chromosome Deletion
ofatumumab
IPI-145
Cell proliferation
Advisory Committees
Hematologic Neoplasms
Chromosomes
Cough
Nausea
Disease-Free Survival
Anemia
Diarrhea
Cell Survival
Fever

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

Cite this

Flinn, I. W., Hillmen, P., Montillo, M., Nagy, Z., Illés, A., Etienne, G., ... Stilgenbauer, S. (2018). The phase 3 DUO trial: Duvelisib vs ofatumumab in relapsed and refractory CLL/SLL. Blood, 132(23), 2446-2455. https://doi.org/10.1182/blood-2018-05-850461

The phase 3 DUO trial : Duvelisib vs ofatumumab in relapsed and refractory CLL/SLL. / Flinn, Ian W.; Hillmen, Peter; Montillo, Marco; Nagy, Zsolt; Illés, A.; Etienne, Gabriel; Delgado, Julio; Kuss, Bryone J.; Tam, Constantine S.; Gasztonyi, Zoltán; Offner, Fritz; Lunin, Scott; Bosch, Francesco; Davids, Matthew S.; Lamanna, Nicole; Jaeger, Ulrich; Ghia, Paolo; Cymbalista, Florence; Portell, Craig A.; Skarbnik, Alan P.; Cashen, Amanda F.; Weaver, David T.; Kelly, Virginia M.; Turnbull, Barry; Stilgenbauer, Stephan.

In: Blood, Vol. 132, No. 23, 06.12.2018, p. 2446-2455.

Research output: Contribution to journalArticle

Flinn, IW, Hillmen, P, Montillo, M, Nagy, Z, Illés, A, Etienne, G, Delgado, J, Kuss, BJ, Tam, CS, Gasztonyi, Z, Offner, F, Lunin, S, Bosch, F, Davids, MS, Lamanna, N, Jaeger, U, Ghia, P, Cymbalista, F, Portell, CA, Skarbnik, AP, Cashen, AF, Weaver, DT, Kelly, VM, Turnbull, B & Stilgenbauer, S 2018, 'The phase 3 DUO trial: Duvelisib vs ofatumumab in relapsed and refractory CLL/SLL', Blood, vol. 132, no. 23, pp. 2446-2455. https://doi.org/10.1182/blood-2018-05-850461
Flinn, Ian W. ; Hillmen, Peter ; Montillo, Marco ; Nagy, Zsolt ; Illés, A. ; Etienne, Gabriel ; Delgado, Julio ; Kuss, Bryone J. ; Tam, Constantine S. ; Gasztonyi, Zoltán ; Offner, Fritz ; Lunin, Scott ; Bosch, Francesco ; Davids, Matthew S. ; Lamanna, Nicole ; Jaeger, Ulrich ; Ghia, Paolo ; Cymbalista, Florence ; Portell, Craig A. ; Skarbnik, Alan P. ; Cashen, Amanda F. ; Weaver, David T. ; Kelly, Virginia M. ; Turnbull, Barry ; Stilgenbauer, Stephan. / The phase 3 DUO trial : Duvelisib vs ofatumumab in relapsed and refractory CLL/SLL. In: Blood. 2018 ; Vol. 132, No. 23. pp. 2446-2455.
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AU - Nagy, Zsolt

AU - Illés, A.

AU - Etienne, Gabriel

AU - Delgado, Julio

AU - Kuss, Bryone J.

AU - Tam, Constantine S.

AU - Gasztonyi, Zoltán

AU - Offner, Fritz

AU - Lunin, Scott

AU - Bosch, Francesco

AU - Davids, Matthew S.

AU - Lamanna, Nicole

AU - Jaeger, Ulrich

AU - Ghia, Paolo

AU - Cymbalista, Florence

AU - Portell, Craig A.

AU - Skarbnik, Alan P.

AU - Cashen, Amanda F.

AU - Weaver, David T.

AU - Kelly, Virginia M.

AU - Turnbull, Barry

AU - Stilgenbauer, Stephan

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