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

Ian W. Flinn, Peter Hillmen, Marco Montillo, Zsolt Nagy, Árpád 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, Amanda F. Cashen, David T. Weaver, Virginia M. Kelly, Barry Turnbull and Stephan Stilgenbauer

Key points

  • Duvelisib significantly improved progression-free survival and overall response rates compared to ofatumumab in RR CLL/SLL patients.

Abstract

Duvelisib (also known as IPI-145) is an oral, dual inhibitor of phosphoinositide 3-kinase (PI3K) δ and -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 versus ofatumumab monotherapy for patients with relapsed or refractory (RR) CLL/SLL. Patients were randomized 1:1 to oral duvelisib 25 mg twice daily (BID) (n = 160) or ofatumumab intravenous (IV) (n = 159). The study met the primary study endpoint by significantly improving progression-free survival (PFS) per Independent Review Committee (IRC) assessment compared to ofatumumab for all patients (median 13.3 months versus 9.9 months; hazard ratio [HR] = 0.52; p < 0.0001), including those with high-risk chromosome 17p13.1 deletions [del(17p)] and/or TP53 mutations (HR = 0.40; p = 0.0002). The overall response rate (ORR) was significantly higher with duvelisib (74% versus 45%; p < 0.0001) regardless of del(17p) status. The most common adverse events (AEs) 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 is registered at ClinicalTrials.gov as NCT02004522.

  • Submitted May 11, 2018.
  • Accepted July 25, 2018.