Clinical Profile of Gilteritinib in Japanese Patients with Relapsed/Refractory AML: an Open-Label Phase 1 Study.

Gilteritinib, a novel, highly specific, potent fms-like tyrosine kinase 3/AXL inhibitor, demonstrated antileukemic activity in patients with relapsed/refractory (R/R) acute myeloid leukemia (AML). In this open-label phase 1 study (NCT02181660), Japanese patients (aged 18years) with R/R AML received once-daily gilteritinib, escalating from 20 to 300mg/d. Primary endpoints were safety/tolerability, including the maximum tolerated dose (MTD) and the recommended dose (RD); secondary endpoints were antileukemic activity and pharmacokinetics (PK). Twenty-four Japanese patients with R/R AML received once-daily oral gilteritinib in 1 of 6 dose-escalation cohorts (20, 40, 80, 120, 200, and 300mg/d). Gilteritinib was well tolerated. The MTD was 200mg/d; dose-limiting toxicities were grade 3 tumor lysis syndrome (120mg/d; n=1); and grade 3 elevated blood lactate dehydrogenase, amylase, blood creatine phosphokinase levels, and syncope (all n=2; 300mg/d). The RD was 120mg/d. The most common drug-related grade 3 adverse events were thrombocytopenia (n=4 [16.7%]) and increased blood creatine phosphokinase (n=3 [12.5%]). Gilteritinib had a dose-proportional PK profile. Among patients with mutated fms-like tyrosine kinase 3, the overall response rate (ORR) was 80% (n=4 of 5; complete remission [CR] with incomplete platelet recovery, 1 [20%]; CR with incomplete hematologic recovery, 2 [40%]; partial remission (PR), 1 [20%]). Among patients with wild-type fms-like tyrosine kinase 3, ORR was 36.4%; (n=4 of 11; CR, 1 [9.1%]; CR with incomplete platelet recovery, 2 [18.2%]; PR, 1 [9.1%]). In conclusion, gilteritinib was well tolerated and demonstrated antileukemic activity in a Japanese R/R AML population.