Study of Iadademstat and Gilteritinib in Patients With R/R AML With FMS-like Tyrosine Kinase Mutation (FLT3 Mut+)

Main Inclusion Criteria:

• Diagnosis of primary AML or AML with myelodysplasia-related changes (AML-MRC)

• Patient is in first or second relapse or has refractory disease. Patients must havehad histologic verification of AML at the original diagnosis.

• Patient must be positive for the following FLT3 mutations in bone marrow or PB: FLT3internal tandem duplication (ITD), FLT3 tyrosine kinase domain (TKD) D835 or I836 orFLT3-ITD and specified FLT3-TKD.

• ECOG performance status 0-2

• Life expectancy of at least 3 months in the opinion of the investigator.

• Normal hepatic and renal function.

• Patient is able to swallow oral medications.

• Female patients are postmenopausal, documented as surgically sterile, use twomethods of contraception or practice true abstinence and have a negative urinepregnancy test at screening.

• Male patients even if surgically sterilized agree to practice true abstinence or usehighly effective barrier contraception.

Main Exclusion Criteria:

• Diagnosis of acute promyelocytic leukemia.

• Known BCR-ABL-positive leukemia.

• AML secondary to prior chemotherapy for other neoplasms (except for MDS).

• AML that has relapsed after or is refractory to more than 2 lines of therapy.

• Clinically active central nervous system leukemia or prior history of NCI CTCAEGrade ≥ 3 drug-related CNS toxicity.

• Major surgery or radiation therapy within 4 weeks prior to the first study dose.

• Prior treatment with iadademstat is not allowed. Treatment with any other agentswith KDM1A/LSD1 inhibitory activity is only allowed if treatment finalized at least 3 weeks prior to first dose on study. Previous treatment with FLT3 inhibitors isallowed in the following cases: midostaurin and sorafenib are allowed when used infirst-line therapy regimen as part of induction, consolidation and/or maintenance:quizartinib and gilteritinib are allowed when used in first-line therapy regimen, aspart of induction, consolidation and/or maintenance, ONLY if patients were notrefractory to the drugs or if responding, relapse did not occur while on thesedrugs.

• Patients not eligible to receive gilteritinib per label.

• Prior treatment with 3 or more lines of AML therapy.

• Treatment with any investigational products within 3 weeks prior to first dose ofstudy treatment.

• Uncontrolled hypertension or poorly controlled diabetes.

• Evidence of active uncontrolled viral, bacterial, or systemic fungal infection.

• Pregnant or lactating women.