APTIVATE: This study is evaluating how safe, tolerable and effective targeted therapy (called tuspetinib) is in people with relapsed or refractory acute myeloid leukaemiaA Phase 1/2 Open Label, Multicenter, Dose Escalation and Expansion Study of the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of HM43239 in Patients With Relapsed or Refractory Acute Myeloid Leukemia (AML)

Exclusion

Patients must not enter the study if any of the following exclusion criteria are fulfilled.

• Patient was diagnosed as acute promyelocytic leukemia (APL)
• Patient has BCR-ABL-positive leukemia
• Patient has an active malignancy other than AML, or Myelodysplastic Syndrome (MDS).
• Patient has persistent non-hematological toxicities of ≥ Grade 2 (CTCAE v4.03), with symptoms and objective findings, from prior AML treatment (including chemotherapy, kinase inhibitors, immunotherapy, experimental agents, radiation, or surgery)

• Patient has had hematopoietic stem cell transplant (HSCT) and meets any of the following:

  1. Has undergone HSCT within the 2 month period prior to the first study dose
  2. Has clinically significant graft-versus-host-disease(GVHD) requiring treatment
  3. Has ≥ Grade 2 persistent non-hematological toxicity related to the transplant
  4. Has a donor lymphocytes infusion (DLI) ≤ 30 days prior to the first study dose or during the first two cycle of treatment on the study.
• Patient has meningeal or central nervous system (CNS) involvement with leukemia or other CNS disease related to underlying and secondary effects of malignancy.
• Patient has disseminated intravascular coagulation abnormality (DIC).
• Patient has had major surgery within 4 weeks prior to the first study dose.
• Patient has had radiation therapy within 4 weeks prior to the first study dose.
• Patient has congestive heart failure New York Heart Association (NYHA) class 3 or 4, or patient with a history of congestive heart failure NYHA class 3 or 4 in the past, unless a screening echocardiogram or multigated acquisition (MUGA) scan performed within 3 months prior to study entry results in a left ventricular ejection fraction (LVEF) that is ≥ 45%.

• Any of the following cardiac abnormalities of history

  1. Patient has any clinically important abnormalities in rhythm, conduction or morphology of resting ECG, e.g., complete left bundle branch block, third-degree heart block, second-degree heart block, or PR interval > 250 milliseconds (ms).
  2. Patient has a mean QT interval (QTc) by Friderica's method (QTcF) > 450ms in three successive Screening measurements.
  3. Patient has any factors that increase the risk of QTc prolongation or risk of arrhythmic events, such as congenital long QT, syndrome, family history of long QT syndrome.
  4. Patient is unable or unwilling to discontinue concomitant use of drugs that are known to prolong the QT interval.
• Patient is known to have active infection including any identified active COVID-19 infection.
• Patient is known to have human immunodeficiency virus infection.
• Patient has known active hepatitis B or C, or other active hepatic disorder.
• Patient has any condition which, in the investigator's opinion, makes the patient unsuitable for study participation.
• Patient has a history of Grade 3 or 4 non-hematologic toxicity related to tyrosine kinase inhibitor.