Phase I/II Trial of the FLT3 Kinase Inhibitor XY0206 in Patients With Relapsed/Refractory Acute Myeloid Leukemia.

This Phase I/II clinical trial (NCT04471064) evaluated the preliminary efficacy, safety, and pharmacokinetics of XY0206, a novel oral FMS-like tyrosine kinase 3 (FLT3) inhibitor, in patients with relapsed or refractory acute myeloid leukemia (R/R AML). From September 2020 to December 2022, this open-label, multicenter study enrolled patients aged ≥ 18 years with R/R AML. The trial included dose-escalation and dose-expansion phases, with six cohorts receiving XY0206 at doses ranging from 12.5 to 62.5 mg once daily or 25 mg twice daily. Of the 61 enrolled participants, 37 had FLT3 mutation-positive (FLT3) AML. The overall response rate (ORR) was 34.4% in the entire cohort and 48.6% in FLT3 patients. Among FLT3 patients, the composite complete remission rate (CRc) was 45.9%, including a complete remission (CR) rate of 5.4% and a CR with partial hematologic recovery (CRh) rate of 13.5% and a CR with incomplete hematologic recovery (CRi) rate of 27.0%. In patients with FLT3 internal tandem duplication (FLT3-ITD) mutations, the ORR was 56.7%, with a CRc of 53.3% (CR: 6.7%; CRh: 16.7% ; CRi: 30.0%). The 37.5 mg dose cohort, identified as the target dose, was expanded exclusively for FLT3 patients. XY0206 exhibited a favorable safety profile and demonstrated potent antileukemic activity, particularly in FLT3 R/R AML patients, supporting its further clinical development. Trial Registration: CTR20201214 (CDE); ClinicalTrials.gov ID: NCT04471064.