KATALYST-HEME-01: Study of the KAT6 Inhibitor MEN2312 in Heme Malignancies

Prior treatment

• Participant received prior treatment with KAT6 inhibitor.
• Participant with relapsed/refractory (R/R) AML who had received previous Chimeric Antigen Receptor T-cell (CAR-T) treatment for an antecedent hematologic disease.
• Participants with active central nervous system (CNS) involvement by AML are excluded. Participants with a history of CNS leukemia are eligible provided that CNS disease has resolved before the first dose of MEN2312, as demonstrated by at least one negative cerebrospinal fluid (CSF) assessment obtained within 7 days before Cycle 1 Day 1.

Other illness

• Participant has a concurrent malignancy or prior malignancy (except myelodysplastic syndromes \[MDS\]) and has not been in remission within the 1-year period before screening.
• Any significant medical condition that, in the opinion of the Investigator, would place the participant at unacceptable risk if they were to participate in the trial.

Other

• Participant has a diagnosis of blastic transformation of chronic myeloid leukemia (CML) or acute promyelocytic leukemia (APL).
• Participant is pregnant or breastfeeding.
  • Note: Other protocol-defined inclusion/exclusion criteria may apply.

• Participant must have a diagnosis of relapsed or refractory acute myeloid leukemia (AML), including de novo or therapy-related AML (tAML) according to World Health Organization (WHO) 2022 and/or International Consensus Classification 2022 (ICC) 2022.
• Participants must have a leukocyte count \< 25,000/microliters (μL) (\< 25 × 10\^9/liter \[L\]) prior to Cycle 1 Day 1.
• Adequate organ function defined as:
  • Renal Function:
• Calculated creatinine clearance (CrCl) \> 50 milliliters (mL)/minute for age-appropriate determination (for example, Cockcroft Gault formula)
  • Hepatic Function:
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3 × upper limit of normal (ULN)
• Total serum bilirubin level \< 1.5 × ULN (unless due to a known history of Gilbert's disease and Direct Bilirubin is within normal limits \[≤ 1 ULN\])
  • Cardiac Function:
• Left ventricular ejection fraction (LVEF) ≥ 50 % or the institutional lower limit of normal, as determined by echocardiogram (ECHO) or multigated acquisition (MUGA) scan performed within 30 days before the first dose of MEN2312.
• No clinically significant uncontrolled cardiac arrhythmia or other clinically significant cardiac condition that, in the opinion of the Investigator, would increase the risk associated with study participation.
  • Performance Status:
• Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2.
• Participants must have recovered to Grade ≤ 1 (or baseline, if clinically appropriate) from clinically significant toxicities of prior anticancer therapy, except for alopecia or toxicities considered irreversible and not expected to increase the risk associated with MEN2312, as determined by the Investigator.
• Participant is able and willing to adhere to the trial visit schedule and other protocol requirements.