MEN1703 (SEL24) in Participants With Acute Myeloid Leukemia

An adverse event (AE) was defined as any new untoward medical occurrence or worsening of a pre-existing medical condition in a participant or clinical investigation participant administered a medicinal product and which does not necessarily have a causal relationship with this treatment. An AE could therefore be any unfavorable and unintended sign (including a clinically significant abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not considered related to the investigational medicinal product. A summary of serious and all other non-serious adverse events regardless of causality is located in the Reported Adverse events module.

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.

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.

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

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.