Duvelisib (IPI-145) is an oral dual inhibitor of phosphoinositide-3-kinase 
(PI3K)-δ and -γ in clinical development for the treatment of hematologic 
malignancies, including indolent non-Hodgkin lymphoma (iNHL). In a Phase 1, 
open-label study to determine the maximum tolerated dose (MTD), 
pharmacokinetics, pharmacodynamics, clinical activity, and safety of duvelisib 
monotherapy in patients with advanced hematologic malignancies, duvelisib was 
administered at eight dose levels (8-100 mg BID) in a dose-escalation phase (n 
= 31 evaluable patients). Two dose-limiting toxicities (DLTs), Grade 3 
transaminase elevations and Grade 3 rash, occurred at 100 mg BID, and the MTD 
was determined to be 75 mg BID. Across all doses, 58.1% of iNHL patients had a 
response (19.4% complete, 35.5% partial, and 3.2% minor); median time to 
response was 1.84 months and duration of response was 16.9 months. Median 
progression-free survival was 14.7 months, and the probability of overall 
survival at 24 months was 71.7%. Severe (Grade ≥ 3) adverse events included 
elevated liver enzymes (38.7%), diarrhea (25.8%), and neutropenia (29.0%). Three 
patients, all in the 75 mg BID cohort, experienced fatal AEs: E. coli sepsis, 
acute respiratory failure, and fungal pneumonia. No iNHL patients experienced 
Pneumocystis pneumonia. Duvelisib demonstrated favorable clinical activity and 
an acceptable safety profile in these high-risk, heavily pretreated, 
relapsed/refractory iNHL patients, with 25 mg BID selected for further clinical 
development.