An open-label phase 2 study of glycogen synthase kinase-3 inhibitor LY2090314 in patients with acute leukemia

This open-label, Phase-2 study investigated the safety of LY2090314 (GSK-3 inhibitor) in AML patients. Twenty patients received 40-mg LY2090314 (50-mg ranitidine pretreatment) as follows: Cohort 1 - days 1, 8, and 15 of a 28-d cycle (n=7); Cohort 2 - days 1, 5, and 9 of a 21-d cycle (n=6); Cohort 3 - days 1, 5, 9, and 12 of a 21-d cycle (n=7). Decreased appetite (n=7) and nausea (n=4) were the most frequently reported possibly drug-related non-hematologic treatment-emergent adverse events (TEAEs). Hematologic TEAEs included febrile neutropenia (n=2), thrombocytopenia (n=1), and anemia (n=1). Atrial flutter (n=1), QT interval prolongation (n=3), and visual disturbances (n=2) were observed, but were not clinically significant (investigator assessed). Although -catenin levels indicated an on-target effect, no complete or partial remissions were observed. Pharmacokinetics were consistent with a previous Phase 1 study. These data suggest that single-agent LY2090314 has acceptable safety but limited clinical benefit in AML patients at the dose/frequencies investigated.