A Phase I/II Study of NMS-03592088, a FLT3, KIT and CSF1R Inhibitor, in Patients with Relapsed or Refractory AML or CMML

Inclusion Criteria:

• Patients with relapsed/refractory disease who have failed standard therapy or are unsuitable for standard treatment, with one the following confirmed diagnosis: AML as 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 administration should be at least 2 weeks for any agents other than hydroxyurea.
• All acute toxic effects (excluding alopecia) of any prior therapy must have resolved to 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 squamous cell skin cancer and/or cone biopsied in situ carcinoma of the cervix uteri and/or superficial bladder cancer.
• Patients with known leukemia involvement of central nervous system (CNS)
• Hematopoietic stem cell transplantation (HSCT) within 3 months of treatment start and/or persistent non-hematologic toxicities of Grade ≥2 related to the transplant
• Active acute or chronic graft versus host disease (GVHD) requiring immunosuppressive treatment
• Patients with QTcF interval ≥ 480 milliseconds or with risk factors for torsade de pointes
• Pregnancy.
• Breast-feeding or planning to breast feed during the study or within 3 months after study treatment.
• Any of the following in the previous 6 months: myocardial infarction, unstable angina, coronary/peripheral artery bypass graft, symptomatic congestive heart failure, cerebrovascular accident or transient ischemic attack, pulmonary embolism, deep vein thrombosis
• Known active, life threatening or clinically significant uncontrolled systemic infection.
• Known active gastrointestinal disease
• Known active gastrointestinal ulcer
• Other severe or chronic medical or psychiatric condition or laboratory abnormality that 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 of myasthenia 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 or receiving treatment for cardiac rhythm disorder or diabetes that is not adequately controlled

Other protocol specific inclusion/exclusion criteria may apply