1. 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
- Author
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O'Brien, Susan, Patel, Manish, Kahl, Brad S, Horwitz, Steven M, Foss, Francine M, Porcu, Pierluigi, Jones, Jeffrey, Burger, Jan, Jain, Nitin, Allen, Kerstin, Faia, Kerrie, Douglas, Mark, Stern, Howard M, Sweeney, Jennifer, Kelly, Patrick, Kelly, Virginia, and Flinn, Ian
- Subjects
Biomedical and Clinical Sciences ,Oncology and Carcinogenesis ,Clinical Trials and Supportive Activities ,Clinical Research ,Hematology ,Orphan Drug ,Rare Diseases ,Lymphoma ,Cancer ,Evaluation of treatments and therapeutic interventions ,6.1 Pharmaceuticals ,Adult ,Aged ,Female ,Humans ,Isoquinolines ,Leukemia ,Lymphocytic ,Chronic ,B-Cell ,Male ,Middle Aged ,Neutropenia ,Phosphoinositide-3 Kinase Inhibitors ,Purines ,Remission Induction ,Transaminases ,Treatment Outcome ,Cardiorespiratory Medicine and Haematology ,Immunology ,Cardiovascular medicine and haematology - 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.
- Published
- 2018