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

This is an escalation/expansion, open label, single arm, study to investigate the safety and the RP2D of the combination of iadademstat with gilteritinib in FLT3-mutated R/R AML.

This study consists of 2 parts. A dose finding part to evaluate the safety, tolerability, pharmacokinetic (PK), pharmacodynamic (PD) and emerging activity of iadademstat and gilteritinib combination, and to determine the pharmacologically-active dose (i.e., the minimum safe and biologically active dose) of iadademstat in combination with gilteritinib, and an expansion part at the specific dose/s selected to evaluate the activity of iadademstat in combination with gilteritinib in patients with FLT3-mutated R/R AML.

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 have had histologic verification of AML at the original diagnosis.
• Patient must be positive for the following FLT3 mutations in bone marrow or PB: FLT3 internal tandem duplication (ITD), FLT3 tyrosine kinase domain (TKD) D835 or I836 or FLT3-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 two methods of contraception or practice true abstinence and have a negative urine pregnancy test at screening.
• Male patients even if surgically sterilized agree to practice true abstinence or use highly 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 CTCAE Grade ≥ 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 agents with 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 is allowed in the following cases: midostaurin and sorafenib are allowed when used in first-line therapy regimen as part of induction, consolidation and/or maintenance: quizartinib and gilteritinib are allowed when used in first-line therapy regimen, as part of induction, consolidation and/or maintenance, ONLY if patients were not refractory to the drugs or if responding, relapse did not occur while on these drugs.
• 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 of study treatment.
• Uncontrolled hypertension or poorly controlled diabetes.
• Evidence of active uncontrolled viral, bacterial, or systemic fungal infection.
• Pregnant or lactating women.