Early clinical activity and pharmacodynamic effects of duvelisib, a PI3K-δ,γ inhibitor, in patients with treatment-naïve CLL.

7074 Background: Signaling via PI3K-δ and PI3K-γ has distinct and complementary effects on malignant B-cells and nonmalignant immune cells in chronic lymphocytic leukemia (CLL). Duvelisib, an oral PI3K-δ,γ inhibitor, has shown clinical activity in a phase 1 study, IPI-145-02. The activity of duvelisib monotherapy in pts with treatment-naive (TN) CLL from this study are reported here. Methods: Following dose escalation, an expansion cohort of TN CLL pts was enrolled (n = 18). Response was based on iwCLL (2008) criteria. Safety included AEs and laboratory assessments. Pharmacodynamic assessments included peripheral blood (PB) flow cytometry for phospho-S473 AKT (pAKT) and Ki67, and measurement of serum chemokines and cytokines. Numbers of PB T-cell subsets were also monitored. Results: As of Oct 2014, 18 TN CLL pts received duvelisib 25 mg BID. The best ORR per iwCLL was 82% (PRs in 14/17 evaluable pts) with a median time on treatment of 53 weeks (range 8-69). Ten pts remain on treatment, while 8 discontinu...