Study of MP0533 in Patients Acute Myeloid Leukemia or Myelodysplastic Syndrome

A Phase 1/2a, First-in-human, Open-label, Multicenter, Dose Escalation Study of MP0533 in Patients With Acute Myeloid Leukemia (AML) or Myelodysplastic Syndrome (MDS)

The purpose of this study is to evaluate the safety, tolerability, and preliminary activity of MP0533 in patients with acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS)

Inclusion Criteria:

• Has signed and dated written informed consent prior to performing any study procedure, including screening
• Diagnosis of relapsed/refractory AML or relapsed/refractory MDS/AML according to the ELN recommendation 2022.
• Age ≥18 years old on the day of signing informed consent
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 to 2
• Anticipated life expectancy ≥ 12 weeks by investigator judgement
• White blood count (WBC) ≤ 15G/L at day of trial drug infusion
• Adequate renal and hepatic function
• Is using highly effective contraception, for females of childbearing potential and for men

Exclusion Criteria:

• Mixed phenotype acute leukemia
• Patients with favorable AML mutations according to ELN recommendation 2022 and 2024
• Allogeneic HCT within the last 3 months and/or eligibility for standard 2nd line of targeted therapy, like gilteritinib for FLT3 mutated AML, unless this therapeutic option has already been given and proven ineffective (patient relapsed or resistant to), or contraindicated, or confounding mutations exist, or there is a lack of access to this recommended therapy.
• More than 2 prior lines of anti-leukemic therapy
• Active GvHD requiring immune-suppressive therapy
• Use of immunosuppressive drugs
• Clinical signs of AML in the central nervous system
• Major surgery within 28 days prior to start of study medication
• Other malignancy requiring active therapy, but adjuvant endocrine therapy is allowed
• Any uncontrolled active infection
• Treatment with investigational agents or agents targeting CD33, CD123 or CD70 within 4 weeks or five times the half-life of the agent, whichever is longer, prior to start of trial medication
• Left ventricular ejection fraction of < 50% on echocardiographic exam at screening
• History or evidence of clinically significant cardiovascular disease
• Pulmonary disease with clinically relevant hypoxia
• Active hepatitis
• Concurrent enrolment in another clinical trial, unless it is an observational (non-interventional) study or it is the follow-up period of an interventional study
• Known hypersensitivity to any of the excipients of the investigational medicinal product (IMP), i.e. finished MP0533 drug

Dose Expansion Group (Arm B in treatment-naïve patients only):

Inclusion

• Treatment-naïve patients who are eligible to AZA+VEN as standard of care

Dose Escalation and Expansion Groups (Arm B only):

Exclusion

1. received VEN in prior treatment lines
2. received strong and/or moderate CYP3A inducers within 7 days before the initiation of AZA/VEN regimen;
3. Has consumed grapefruit, grapefruit products, Seville oranges or Starfruit within 3 days before the initiation of AZA/VEN regimen;
4. Has a malabsorption syndrome or other condition that precludes the enteral route of administration of VEN.