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.