Final Results of a Phase 1/2 Study of SYK Inhibitor Entospletinib in Combination with Obinutuzumab in Patients with Relapsed/Refractory (R/R) Chronic Lymphocytic Leukemia (CLL)

Therapeutic resistance and intolerance of Bruton tyrosine kinase (BTK) inhibitors is an emerging need in CLL. SYK is integral to the activation of BTK and the B-cell receptor (BCR) signaling cascade and is overexpressed in CLL. We have shown that BAFF-mediated SYK activation triggered BCR signaling and rendered protection of CLL cells from spontaneous apoptosis in vitro. Single agent small molecule SYK inhibitor entospletinib was efficacious in treatment of patients with R/R CLL. Here we report final results of a single arm, open label, investigator-initiated phase 1/2 clinical trial which evaluated safety and efficacy of entospletinib in combination with obinutuzumab, a glycoengineered monoclonal anti-CD20 antibody, in patients with R/R CLL (NCT03010358).