This Phase Ib trial is evaluating how safe a targeted therapy (lemzoparlimab) is when used with other cancer treatments (azacitidine and/or venetoclax) in people with acute myeloid leukaemia or myelodysplastic syndrome.A Phase 1b Dose Escalation Study of Lemzoparlimab in Combination With Venetoclax and/or Azacitidine in Subjects With Acute Myeloid Leukemia (AML) or Myelodysplastic Syndrome (MDS)

Inclusion

• Documented confirmation of acute myeloid leukemia (AML) according to the World Health Organization (WHO) criteria, previously untreated [OR]
• Documented diagnosis of previously untreated de novo myelodysplastic syndrome (MDS) according to the 2017 WHO classification with presence of < 20% bone marrow blasts per marrow biopsy/aspirate.

• Participants with documented MDS must meet the following disease activity criteria:

  • Overall revised international prognostic scoring system (IPSS-R) score > 3 (intermediate, high, or very high);
  • Eastern cooperative oncology group (ECOG) performance status of 0 to 2;
  • Hematopoietic stem cell transplant (HSCT) ineligible, or participant who chooses not to undergo HSCT.

• Participants with documented AML with adverse cytogenetic and/or molecular risk, and must be considered ineligible for induction therapy defined by the following:

  • >= 75 years of age; [OR]

  • >= 18 to 74 years of age with at least one of the following comorbidities: --- Eastern cooperative oncology group (ECOG) performance status of 2 to 3; --- Cardiac history of congestive heart failure requiring treatment or ejection fraction <= 50% or chronic stable angina;

    • Diffusion capacity of lung (DLCO) <= 65% or forced expiratory volume during the first second (FEV1) <= 65%;
    • Creatinine clearance >= 30 mL/min to < 45 mL/min;
    • Moderate hepatic impairment with total bilirubin > 1.5 to <= 3.0 × upper limit of normal (ULN);
    • Any other comorbidity that the physician judges to be incompatible with intensive chemotherapy or the participant declines to receive intensive chemotherapy.

Japan Safety Lead-In Phase:

• Documented confirmation of AML according to WHO criteria, relapsed or refractory (R/R) disease without other standard of care treatments.
• Documented diagnosis of MDS according to the 2017 WHO classification with presence of < 20% bone marrow blasts per marrow biopsy/aspirate, with intermediate- and high-risk relapsed/refractory MDS.

• Documented MDS must meet the following disease activity criteria:

  • ECOG performance status of 0 to 2.