MEN1703 (SEL24) in Participants With Acute Myeloid Leukemia

Browse trials for

• Leukemia 5,446
• Leukemia, Myeloid 2,450
• Leukemia, Myeloid, Acute 2,968

Keywords

• AML
• Relapsed/Refractory Acute Myeloid Leukemia
• IDH

Study arms

• Experimental
  Cohort 1 (25 mg)

  Participants received MEN1703 (25 milligrams \[mg\]) orally once daily for 14 consecutive days in cycles of 21 days.

  Drug: MEN1703

• Experimental
  Cohort 2 (50 mg)

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

  Drug: MEN1703

• Experimental
  Cohort 3 (75 mg)

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

  Drug: MEN1703

• Experimental
  Cohort 4 (100 mg)

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

  Drug: MEN1703

• Experimental
  Cohort 5 (125 mg)

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

  Drug: MEN1703

• Experimental
  Cohort 6 (150 mg)

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

  Drug: MEN1703

Interventions

• DrugMEN1703

  MEN1703 given as oral capsules once daily for 14 consecutive days over a 21-day treatment cycle.

  Also known as: SEL24-B489, SEL24

Primary outcomes

1. Part 1 and Part 2: Number of Participants Experiencing Treatment-emergent Adverse Events

   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.

   Time frame: Up to 21 months

2. Part 1: Number of Participants Experiencing Dose-limiting Toxicity (DLT)

   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.

   Time frame: Day 1 through Day 21 (first treatment cycle)

Secondary outcomes

1. Part 1 and Part 2: Overall Response Rate (ORR)

   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.

   Time frame: Up to 32 months

2. Part 1 and Part 2: Partial Remission (PR) Rate

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

   Time frame: Up to 32 months

3. Part 1 and Part 2: Duration of Response (DoR)

   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.

   Time frame: Up to 32 months

4. Part 1 and Part 2: Relapse Free Survival (RFS)

   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.

   Time frame: Up to 32 months

5. Part 1 and Part 2: Overall Survival (OS)

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

   Time frame: Up to 32 months

6. Part 1 and Part 2: Event Free Survival (EFS)

   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.

   Time frame: Up to 32 months

7. Part 1 and Part 2: Transfusion Conversion Rate

   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.

   Time frame: Up to 21 months

8. Part 1 and Part 2: Transfusion Maintenance Rate

   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.

   Time frame: Up to 21 months

9. Part 1 and Part 2: Allogeneic Hematopoietic Stem Cell Transplantation (HSCT) Rate

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

   Time frame: Up to 21 months

10. Part 1 and Part 2: Percentage of Participants With ≥ 50% Bone Marrow Blast Reduction

    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.

    Time frame: Up to 20 months

11. Part 1 and Part 2: Maximum Observed Concentration (Cmax) for MEN1703

    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.

    Time frame: Day 1 and Day 14 of Cycle 1 (pre-dose, up to 120 hours post dose) (21 days/cycle)

12. Part 1 and Part 2: Area Under the Concentration Versus Time Curve From Time Zero to the Last Quantifiable Concentration (AUClast) for MEN1703

    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.

    Time frame: Day 1 of Cycle 1 (pre-dose, up to 24 hours post dose) (21 days/cycle)

13. Part 1 and Part 2: Area Under the Concentration Versus Time Curve From Time Zero to 24 Hours (AUC0-24) for MEN1703

    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.

    Time frame: Day 14 of Cycle 1 (pre-dose, up to 120 hours post dose) (21 days/cycle)

Baseline characteristics

Study documents

• Study protocol · Jun 27, 2022
• Statistical analysis plan · May 10, 2023

Documents are hosted by the registry — open the source record to download them.

Individual participant data

Plan to share: No