HDM201 Added to CT in R/R or Newly Diagnosed AML

Exclusion Criteria

• •Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) that is 0 - 2.
• •Adequate organ functions
• •Left ventricular ejection fraction \> 45%
• •For 1L AML population:
• •For Part 1 or Part 2 Expansion Cohorts 1 or 2: subjects with de novo AML suitable for induction treatment with cytarabine and anthracyclines as per investigator judgement
• •For Part 2 Expansion Cohort 2: documented presence of FLT3 mutation (ITD or TKD ) and suitable for midostaurin treatment as per investigator judgement.
• •For Part 2 Expansion Cohort 3: Subjects with secondary AML (e.g. AML-MRC , secondary to myelodysplasia/MDS or therapy-related AML). Prior use of hypomethylating agents or other therapies with curative intent for treatment previous hematological malignancies or therapy-related AML is allowed. Subjects suitable for induction treatment with liposomal cytarabine/daunorubicin as per investigator judgement.
• •For R/R AML population:
• •All Parts: Diagnosis of relapsed or refractory AML and suitable for treatment with IDAC as per investigator judgement.
• •For Part 3 only: willingness and suitability to participate in DDI Cohort 1 or 2.
• •Prior exposure to MDM2 and MDM4 inhibitor (e.g. idasanutlin)
• •Known symptomatic CNS leukemia not controlled by adequate therapy.
• •Isolated extramedullary leukemia
• •Subjects with prior malignancy (some exceptions apply)
• •QTcF \> 470 ms at screening
• •Subjects who require treatment with moderate or strong CYP3A4 inducers within 14 days prior to starting study treatment or during the study
• •Subjects who require use of herbal preparations/medications and dietary supplements within 7 days prior to first dose and during the study
• •Subjects who require treatment with substrates of CYP3A4/5 with narrow therapeutic index (within 24 hours prior to during and 48 hours after HDM201 administration)
• •Subjects who require treatment with moderate or strong CYP3A4 inhibitors within 48 hours prior to, during and 48 hours post HDM201 administration. (except for Part 3 DDI Cohort 1 and 2)
• •Subject is pregnant or breastfeeding
• •WOCBP unless using highly effective methods of contraception during study treatment and for an appropriate time period after last study treatment
• •Sexually active males unless they use a condom during intercourse while taking study drug and for an appropriate time period after last study treatment
• •For Part 1 only:
• •\- Subjects with a known favorable risk AML subtype at screening or subjects with FLT3 mutation
• •For Part 3 only:
• •DDI Cohort 1: use of posaconazole (other than the planned dosing required by the protocol) within 7 days prior to start of the DDI investigation and for the duration of the DDI period
• •DDI Cohort 2: use of midazolam (other than the planned dosing required by the protocol) within 2 days prior to start of the DDI investigation and for the duration of the DDI period
• •DDI Cohort 1 and 2: subjects who have received, or are expected to receive moderate or strong inhibitors of CYP3A4 within 7 days prior to start of the DDI investigation, for the duration of the investigation, and 24 hours after last blood sample collection for PK assessment
• •Other protocol-defined inclusion/exclusion may apply.