Study of NMS-03592088 in Patients With Relapsed or Refractory AML or CMML

Inclusion Criteria:

• Patients with relapsed/refractory disease who have failed standard therapy or areunsuitable for standard treatment, with one the following confirmed diagnosis: AMLas defined by the European LeukemiaNet (ELN)

• Patients with confirmed diagnosis of AML as defined by the 2022 ELN recommendations

• Patients must have failed standard of care.

• Adult (age ≥ 18 years) patients

• Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2

• The interval from prior antitumor treatment to time of NMS-03592088 administrationshould be at least 2 weeks for any agents other than hydroxyurea.

• All acute toxic effects (excluding alopecia) of any prior therapy must have resolvedto NCI CTCAE version 5.0 Grade ≤1

• Adequate hepatic and renal function

• Patients must use highly effective contraception.

• Signed and dated IEC or IRB-approved informed consent form.

Exclusion Criteria:

• Current enrollment in another interventional clinical study

• Diagnosis of acute promyelocytic leukemia or Breakpoint cluster region-Abelson (BCR-ABL)-positive leukaemia

• Currently active second malignancy, except for adequately treated basal or squamouscell skin cancer and/or cone biopsied in situ carcinoma of the cervix uteri and/orsuperficial bladder cancer.

• Patients with known leukemia involvement of central nervous system (CNS)

• Hematopoietic stem cell transplantation (HSCT) within 3 months of treatment startand/or persistent non-hematologic toxicities of Grade ≥2 related to the transplant

• Active acute or chronic graft versus host disease (GVHD) requiring immunosuppressivetreatment

• Patients with QTcF interval ≥ 480 milliseconds or with risk factors for torsade depointes

• Pregnancy.

• Breast-feeding or planning to breast feed during the study or within 3 months afterstudy treatment.

• Any of the following in the previous 6 months: myocardial infarction, unstableangina, coronary/peripheral artery bypass graft, symptomatic congestive heartfailure, cerebrovascular accident or transient ischemic attack, pulmonary embolism,deep vein thrombosis

• Known active, life threatening or clinically significant uncontrolled systemicinfection.

• Known active gastrointestinal disease

• Known active gastrointestinal ulcer

• Other severe or chronic medical or psychiatric condition or laboratory abnormalitythat may increase the risk associated with study participation.

• Known diagnosis of myasthenia gravis

US only:

• Signs or symptoms of myasthenia gravis or stroke during screening

• Patients with myasthenia gravis specific autoantibodies or any known history ofmyasthenia gravis (MG) autoantibodies at screening window

• Concomitant medications with the potential to cause de novo myasthenia gravis,worsening of myasthenia gravis or cause myasthenia gravis-like symptoms

• Uncontrolled hypertension, atrial fibrillation or flutter, ventricular arrhythmia orreceiving treatment for cardiac rhythm disorder or diabetes that is not adequatelycontrolled

Other protocol specific inclusion/exclusion criteria may apply