Entospletinib (GS-9973) is an orally bioavailable, selective inhibitor of spleen tyrosine kinase (Syk), which is a mediator of B-cell receptor signaling. Sharman and colleagues reported preliminary results of a phase 2 trial of entospletinib monotherapy (800 mg twice daily) in 56 patients with chronic lymphocytic leukemia (CLL; n = 41) and small lymphocytic lymphoma (SLL; n = 15).1
Overall, all patients experienced adverse events (AEs) of any grade. The most common all-grade treatment-emergent adverse events (AEs) were fatigue, nausea, diarrhea, cough, dizziness, headache, pyrexia, decreased appetite, upper respiratory tract infection, and constipation. Grade 3/4 AEs included fatigue (7%), nausea (2%), dizziness (2%), and decreased appetite (2%). Common grade 3/4 laboratory abnormalities included increased aspartate transaminase (5%), increased alanine transaminase (4%), increased total bilirubin (16%), anemia (7%), and neutropenia (29%). Overall, 11 patients discontinued due to AE and 6 deaths were reported. In the evaluable patients, the Independent Review Committee-assessed overall response rate was 57%, with all patients achieving a partial response. Moreover, 38 (73%) patients achieved a decrease of ?50% in tumor bulk. Among the 35 responding patients, median duration of response was 19.0 months. At a median follow-up of 7.5 months, the primary end point of progression-free survival (PFS) at 24 weeks was 69%, median PFS was 19.3 months. Based on these preliminary results, the authors concluded that single-agent entospletinib was well-tolerated and demonstrated activity in patients with CLL/SLL comparable to other BCR pathway inhibitors.
