Entrectinib in Combination With ASTX727 for the Treatment of Relapsed/Refractory TP53 Mutated Acute Myeloid Leukemia

PRIMARY OBJECTIVE: I. To determine the maximum tolerated dose (MTD) of decitabine and cedazuridine (ASTX727) combined with entrectinib in relapsed/refractory (R/R) AML patients with TP53 mutations. SECONDARY OBJECTIVE: I. To assess overall safety and preliminary anti-AML activity of combined ASTX727 and entrectinib regimen. EXPLORATORY OBJECTIVE: I. To assess the potential pharmacodynamic changes observed with treatment consisting of entrectinib alone and in combination with decitabine. OUTLINE: This is a dose-escalation study of entrectinib. Patients receive entrectinib orally (PO) once daily (QD) on days 1-28 and ASTX727 PO QD on days 1-5. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up at 30 days and then every 3 months for up to 1 year.