Ko-Men: A study investigating the benefits and risks of adding ziftomenib targeted therapy to standard of care treatment in people with acute myeloid leukaemia with certain genetic mutations who have not received any treatmentPhase 3 Randomized, Double-blind, Placebo-controlled Studies Assessing Ziftomenib in Combination With Either Standard of Care Nonintensive (Venetoclax+Azacitidine) or Intensive (7+3) Therapy in Patients With Untreated NPM1 Mutated or KMT2A Rearranged Acute Myeloid Leukemia

Inclusion

The following criteria apply to both the Nonintensive Therapy Study and the Intensive Therapy Study unless otherwise noted:

• Age ≥18 years at time of signing the informed consent form.
• Diagnosis of AML per the 2022 WHO Classification of Hematolymphoid Tumors (5th Edition).
• Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2.
• Adequate liver and kidney function according to protocol requirements.
• A female of childbearing potential must agree to use adequate contraception from the time of screening through 180 days following the last dose of study intervention. A male with a female partner of childbearing potential must agree to use abstinence or adequate contraception from the time of screening through 90 days following the last dose of study intervention.

• NONINTENSIVE THERAPY STUDY ONLY (VEN+AZA):

  1. Documented NPM1-m.

  2. Patients considered ineligible for Intensive Therapy defined by the following:

     • i. Age ≥75, OR
     • ii. Age <75 with an ECOG performance status of 2 or cardiac, renal, or kidney impairment per protocol criteria.

• INTENSIVE THERAPY STUDY ONLY (7+3):

  1. Documented NPM1-m or KMT2A-r (KMT2A-r patients with a partial tandem duplication are not eligible).
  2. Documented FLT3 wild-type or ITD ratio <0.05 OR ineligible to receive FLT3-targeted therapy (medically ineligible or mutation in which FLT3 inhibition is not SOC). Lack of access to an FLT3 inhibitor is not considered "ineligible" for FLT3-targeted therapy.
  3. Ejection fraction of ≥50%.
  4. Fit for Intensive Therapy per Investigator opinion.