DoR was defined as the time from the date of first CR, CRi, CRh, CR without minimal residual disease (CRMRD-), MLFS or PR until the date of documented relapse of any type, progressive disease or death due to disease progression for participants who achieve CR, CRi, CRh, CRMRD-, MLFS or PR. Results are reported in days.

RFS was defined as the time from the date of first CR, CRi, CRh, or CRMRD- until the date of documented relapse or death from any cause. Results are reported in days.

OS was defined as the number of days between the first study drug administration and death from any cause. Results are reported in days.

EFS was defined as the time from the date of first study drug intake until the date of documented relapse, treatment failure, or death from any cause. Results are reported in days.

Transfusion conversion rate was defined as the percentage of participants who were transfusion dependent at baseline but became transfusion independent post-baseline. Participants were classified as baseline transfusion independent if there were no red blood cells (RBC) or platelet transfusions at baseline; otherwise, the participant was considered as baseline transfusion dependent. Participants were classified post-baseline transfusion independent in the event of 56 consecutive days without any RBC or platelet transfusion post-baseline; otherwise, the participant was considered post-baseline transfusion dependent.

Transfusion maintenance rate was defined as the percentage of participants who were transfusion independent at baseline and still maintained to be transfusion independent post-baseline. Participants were classified as baseline transfusion independent if there were no RBC or platelet transfusions at baseline; otherwise, the participant was considered as baseline transfusion dependent. Participants were classified post-baseline transfusion independent in the event of 56 consecutive days without any RBC or platelet transfusion post-baseline; otherwise, the participant was considered post-baseline transfusion dependent.

Allogeneic HSCT rate was defined as the percentage of participants undergoing allogeneic stem cell transplant during the study period of each participant.

Bone marrow aspirates/biopsies were taken at designated timepoints for evaluation of leukemic blast proportion in the bone marrow. A reduction in bone marrow blast proportion indicates increased anti-leukemic activity of the study drug.

Nominal blood samples were taken at designated timepoints for evaluation of concentration levels of MEN1703 in plasma. Results are reported as nanograms/milliliter (ng/mL). Standard error not reported, arithmetic coefficient of variation (CV%) reported instead.

Nominal blood samples were taken at designated timepoints for evaluation of concentration levels of MEN1703 in plasma. AUClast was calculated by the linear trapezoidal rule. Results are reported in hour times nanograms/milliliter (h*ng/mL). Standard error not reported, arithmetic CV% reported instead.

Nominal blood samples were taken at designated timepoints for evaluation of concentration levels of MEN1703 in plasma. AUC0-24 was calculated by the linear trapezoidal rule. Results are reported in h*ng/mL. Standard error not reported, arithmetic CV% reported instead.

Safety Population

Participants received MEN1703 (75 mg) orally once daily for 14 consecutive days in cycles of 21 days.

Participants received MEN1703 (100 mg) orally once daily for 14 consecutive days in cycles of 21 days.

Participants received MEN1703 (125 mg) orally once daily for 14 consecutive days in cycles of 21 days.

Participants received MEN1703 (150 mg) orally once daily for 14 consecutive days in cycles of 21 days.

Total of all reporting groups

Participants received MEN1703 (50 mg) orally once daily for 14 consecutive days in cycles of 21 days.

Participants received MEN1703 (75 mg) orally once daily for 14 consecutive days in cycles of 21 days.

Participants received MEN1703 (100 mg) orally once daily for 14 consecutive days in cycles of 21 days.

Participants received MEN1703 (125 mg) orally once daily for 14 consecutive days in cycles of 21 days.

Participants received MEN1703 (150 mg) orally once daily for 14 consecutive days in cycles of 21 days.

AEs were graded according to the National Cancer Institute common terminology criteria for adverse events, version 4.03. The following AEs were considered as DLT unless they were clearly and incontrovertibly attributable to the underlying disease or to an extraneous cause: Grade 5 toxicity; Grade 4 neutropenia lasting ≥42 days from the start of the therapy cycle in absence of evidence of active acute myeloid leukemia (AML) (<5% blasts); Grade 3 or 4 non-hematologic toxicity (with protocol-define exceptions). Only clinically significant abnormalities in laboratory findings, physical examination, vital signs, weight, or electrocardiogram were considered for DLT assessment.

Safety Population: all participants that received at least one dose of MEN1703. Here, 'Overall Number of Participants Analyzed' signifies those participants from Part 1 who were evaluable for this outcome measure.

ORR was defined as the percentage of participants who had a complete remission (CR), complete remission with incomplete hematologic recovery (CRi), complete remission with partial hematologic recovery (CRh), or morphologic leukemia-free state (MLFS) response to therapy.

Efficacy Population: all participants in each cohort that have completed 1 cycle of treatment (considering both the treatment and the washout period) and have taken at least 75% of the study drug during the first cycle. Here, 'Overall Number of Participants Analyzed' signifies those participants who were evaluable for this Outcome Measure.

PR rate was defined as the percentage of participants who had a partial remission response to therapy.

Efficacy Population: all participants in each cohort that have completed 1 cycle of treatment (considering both the treatment and the washout period) and have taken at least 75% of the study drug during the first cycle. Here, 'Overall Number of Participants Analyzed' signifies those participants who were evaluable for this Outcome Measure.

DoR was defined as the time from the date of first CR, CRi, CRh, CR without minimal residual disease (CRMRD-), MLFS or PR until the date of documented relapse of any type, progressive disease or death due to disease progression for participants who achieve CR, CRi, CRh, CRMRD-, MLFS or PR. Results are reported in days.

Efficacy Population: all participants in each cohort that have completed 1 cycle of treatment (considering both the treatment and the washout period) and have taken at least 75% of the study drug during the first cycle. Here, 'Overall Number of Participants Analyzed' signifies those participants who were evaluable for this Outcome Measure.

RFS was defined as the time from the date of first CR, CRi, CRh, or CRMRD- until the date of documented relapse or death from any cause. Results are reported in days.

Efficacy Population: all participants in each cohort that have completed 1 cycle of treatment (considering both the treatment and the washout period) and have taken at least 75% of the study drug during the first cycle. Here, 'Overall Number of Participants Analyzed' signifies those participants who were evaluable for this Outcome Measure.

OS was defined as the number of days between the first study drug administration and death from any cause. Results are reported in days.

Efficacy Population: all participants in each cohort that have completed 1 cycle of treatment (considering both the treatment and the washout period) and have taken at least 75% of the study drug during the first cycle. Here, 'Overall Number of Participants Analyzed' signifies those participants who were evaluable for this Outcome Measure.

EFS was defined as the time from the date of first study drug intake until the date of documented relapse, treatment failure, or death from any cause. Results are reported in days.

Efficacy Population: all participants in each cohort that have completed 1 cycle of treatment (considering both the treatment and the washout period) and have taken at least 75% of the study drug during the first cycle. Here, 'Overall Number of Participants Analyzed' signifies those participants who were evaluable for this Outcome Measure.

Transfusion conversion rate was defined as the percentage of participants who were transfusion dependent at baseline but became transfusion independent post-baseline. Participants were classified as baseline transfusion independent if there were no red blood cells (RBC) or platelet transfusions at baseline; otherwise, the participant was considered as baseline transfusion dependent. Participants were classified post-baseline transfusion independent in the event of 56 consecutive days without any RBC or platelet transfusion post-baseline; otherwise, the participant was considered post-baseline transfusion dependent.

Efficacy Population: all participants in each cohort that have completed 1 cycle of treatment (considering both the treatment and the washout period) and have taken at least 75% of the study drug during the first cycle. Here, 'Overall Number of Participants Analyzed' signifies those participants who were transfusion dependent at baseline and had transfusion status reported post baseline. Data was collected only for Cohort 5 for this end point as pre-specified in the protocol.

Transfusion maintenance rate was defined as the percentage of participants who were transfusion independent at baseline and still maintained to be transfusion independent post-baseline. Participants were classified as baseline transfusion independent if there were no RBC or platelet transfusions at baseline; otherwise, the participant was considered as baseline transfusion dependent. Participants were classified post-baseline transfusion independent in the event of 56 consecutive days without any RBC or platelet transfusion post-baseline; otherwise, the participant was considered post-baseline transfusion dependent.

Efficacy Population: all participants in each cohort that have completed 1 cycle of treatment (considering both the treatment and the washout period) and have taken at least 75% of the study drug during the first cycle. Here, 'Overall Number of Participants Analyzed' signifies those participants who were transfusion independent at baseline and had transfusion status reported post baseline. Data was collected only for Cohort 5 for this end point as pre-specified in the protocol.

Allogeneic HSCT rate was defined as the percentage of participants undergoing allogeneic stem cell transplant during the study period of each participant.

Efficacy Population: all participants in each cohort that have completed 1 cycle of treatment (considering both the treatment and the washout period) and have taken at least 75% of the study drug during the first cycle. Here, 'Overall Number of Participants Analyzed' signifies those participants who were evaluable for this outcome measure. Data was collected only for Cohort 5 for this end point as pre-specified in the protocol.

Bone marrow aspirates/biopsies were taken at designated timepoints for evaluation of leukemic blast proportion in the bone marrow. A reduction in bone marrow blast proportion indicates increased anti-leukemic activity of the study drug.

Efficacy Population: all participants in each cohort that have completed 1 cycle of treatment (considering both the treatment and the washout period) and have taken at least 75% of the study drug during the first cycle. Here, 'Overall Number of Participants Analyzed' signifies those participants who had an available baseline bone marrow assessment and at least 1 post-baseline bone marrow assessment.

Nominal blood samples were taken at designated timepoints for evaluation of concentration levels of MEN1703 in plasma. Results are reported as nanograms/milliliter (ng/mL). Standard error not reported, arithmetic coefficient of variation (CV%) reported instead.

Pharmacokinetics (PK) Population: all participants who received any dose of MEN1703 and had at least 1 measurable drug concentration. Here, 'Number Analyzed' signifies those participants who were evaluable for this outcome measure at the specified time points.

Nominal blood samples were taken at designated timepoints for evaluation of concentration levels of MEN1703 in plasma. AUClast was calculated by the linear trapezoidal rule. Results are reported in hour times nanograms/milliliter (h*ng/mL). Standard error not reported, arithmetic CV% reported instead.

Pharmacokinetics (PK) Population: all participants who received any dose of MEN1703 and had at least 1 measurable drug concentration. Here, 'Overall Number of Participants Analyzed' signifies those participants who were evaluable for this outcome measure at the specified time points.

Nominal blood samples were taken at designated timepoints for evaluation of concentration levels of MEN1703 in plasma. AUC0-24 was calculated by the linear trapezoidal rule. Results are reported in h*ng/mL. Standard error not reported, arithmetic CV% reported instead.

Pharmacokinetics (PK) Population: all participants who received any dose of MEN1703 and had at least 1 measurable drug concentration. Here, 'Overall Number of Participants Analyzed' signifies those participants in Cohorts 2-6 who were evaluable for this outcome measure at the specified time point. Data was not collected for Cohort 1 for this outcome measure.

Participants received MEN1703 (50 mg) orally once daily for 14 consecutive days in cycles of 21 days.

Participants received MEN1703 (75 mg) orally once daily for 14 consecutive days in cycles of 21 days.

Participants received MEN1703 (100 mg) orally once daily for 14 consecutive days in cycles of 21 days.

Participants received MEN1703 (125 mg) orally once daily for 14 consecutive days in cycles of 21 days.

Participants received MEN1703 (150 mg) orally once daily for 14 consecutive days in cycles of 21 days.