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Clinical Trial
. 2018 Nov;93(11):1318-1326.
doi: 10.1002/ajh.25243. Epub 2018 Oct 20.

Duvelisib, an oral dual PI3K-δ,γ inhibitor, shows clinical and pharmacodynamic activity in chronic lymphocytic leukemia and small lymphocytic lymphoma in a phase 1 study

Susan O'Brien  1 , Manish Patel  2 , Brad S Kahl  3 , Steven M Horwitz  4 , Francine M Foss  5 , Pierluigi Porcu  6 , Jeffrey Jones  6 , Jan Burger  1 , Nitin Jain  1 , Kerstin Allen  7 , Kerrie Faia  7 , Mark Douglas  7 , Howard M Stern  7 , Jennifer Sweeney  7 , Patrick Kelly  7 , Virginia Kelly  7 , Ian Flinn  8
Affiliations
Clinical Trial

Duvelisib, an oral dual PI3K-δ,γ inhibitor, shows clinical and pharmacodynamic activity in chronic lymphocytic leukemia and small lymphocytic lymphoma in a phase 1 study

Susan O'Brien et al. Am J Hematol. 2018 Nov.

Abstract

Duvelisib (IPI-145), an oral, dual inhibitor of phosphoinositide-3-kinase (PI3K)-δ and -γ, was evaluated in a Phase 1 study in advanced hematologic malignancies, which included expansion cohorts in relapsed/refractory (RR) chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL) and treatment-naïve (TN) CLL. Per protocol, TN patients were at least 65 years old or had a del(17p)/TP53 mutation. Duvelisib was administered twice daily (BID) in 28-day cycles at doses of 8-75 mg in RR patients (n = 55) and 25 mg in TN patients (n = 18.) Diarrhea was the most common nonhematologic AE (TN 78%, RR 47%); transaminase elevations the most frequent lab-abnormality AE (TN 33.3%, RR 30.9%); and neutropenia the most common ≥grade 3 AE (RR 44%, TN 33%). The overall response rates were 56.4% for RR patients (1.8% CR, 54.5% PR) and 83.3% for TN patients (all PRs); median response duration was 21.0 months in RR patients but was not reached for TN patients. Based upon phase 1 efficacy, pharmacodynamics, and safety, duvelisib 25 mg BID was selected for further investigation in a phase 3 study in RR CLL/SLL.

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Conflict of interest statement

CONFLICT OF INTERESTS

S.O., M.P., B.K., S.H, F.F., P.P., J.J., J.B., N.J., and I.F. declare no competing financial interests. Authors K.A., K.F., M.D., H.M.S., J.S., P.K., and V.K. were employees of Infinity Pharmaceuticals at the time of study conduct.

Figures

FIGURE 1
FIGURE 1
Progression-free survival and overall survival in patients with relapsed/refractory CLL/SLL
See this image and copyright information in PMC

References

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