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Phase I/II Trial of the FLT3 Kinase Inhibitor XY0206 in Patients With Relapsed/Refractory Acute Myeloid Leukemia
Lin Song1, Xudong Wei2, Zhimin Zhai3
1National Clinical Research Center for Blood Diseases, State Key Laboratory of Experimental Hematology, Haihe Laboratory of Cell Ecosystem, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, China.
Abstract:
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 (FLT3mut+) AML. The overall response rate (ORR) was 34.4% in the entire cohort and 48.6% in FLT3mut+ patients. Among FLT3mut+ 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 FLT3mut+ patients. XY0206 exhibited a favorable safety profile and demonstrated potent antileukemic activity, particularly in FLT3mut+ R/R AML patients, supporting its further clinical development. Trial Registration: CTR20201214 (CDE); ClinicalTrials.gov ID: NCT04471064.
Insights
This Phase I/II trial investigated XY0206, a novel FMS-like tyrosine kinase 3 (FLT3) inhibitor, for relapsed or refractory acute myeloid leukemia (R/R AML). XY0206 showed promising efficacy and safety, especially in FLT3 mutation-positive patients.
Area of Science:
- Hematology
- Oncology
- Pharmacology
Background:
- Relapsed or refractory acute myeloid leukemia (R/R AML) presents significant treatment challenges.
- FMS-like tyrosine kinase 3 (FLT3) mutations are common in AML and associated with poor prognosis.
- Targeted therapies inhibiting FLT3 are a focus in AML treatment development.
Purpose of the Study:
- To evaluate the preliminary efficacy, safety, and pharmacokinetics of XY0206, an oral FLT3 inhibitor.
- To determine the optimal dose and assess the activity of XY0206 in patients with R/R AML.
- To specifically investigate the response in patients with FLT3 mutations.
Main Methods:
- Phase I/II, open-label, multicenter clinical trial (NCT04471064).
- Dose-escalation and dose-expansion phases involving six cohorts of R/R AML patients.
- Administration of XY0206 at various daily or twice-daily doses.
Main Results:
- Overall response rate (ORR) was 34.4% in all patients and 48.6% in FLT3 mutation-positive (FLT3mut+) patients.
- Composite complete remission (CRc) rate was 45.9% in FLT3mut+ patients, including CR, CRh, and CRi.
- Patients with FLT3 internal tandem duplication (FLT3-ITD) mutations showed an ORR of 56.7% and CRc of 53.3%.
Conclusions:
- XY0206 demonstrated potent antileukemic activity, particularly in FLT3mut+ R/R AML.
- The drug exhibited a favorable safety profile.
- These findings support the further clinical development of XY0206 for FLT3mut+ R/R AML.
