S243249 Monotherapy in Patients With Relapsed or Refractory Acute Leukemia With a KMT2A or NUP98 Translocation or Relapsed or Refractory AML With NPM1c Mutation

NCT07722312 | Not Yet Recruiting Phase 1 DMC FDA Drug

• 2 other identifiers: BN104-1022025-524689-74-00
• Study Type: interventional
• Target: 80
• Locations: 0 countries
• Sites: N/A

Brief Summary

The objective of this study is to establish the efficacy, safety, and tolerability of S243249 and to establish the recommended phase 2 dose (RP2D) of S243249 monotherapy in participants with relapsed/refractory (R/R) acute leukemia with select mutations. Phase 1 dose optimization will determine the RP2D to be used in Phase 2 dose expansion. The study will include a screening period, a treatment period consisting of continuous 28-day cycles of treatment, a safety follow-up period and a long-term follow-up period. Participants may undergo blood tests, electrocardiogram (ECG), bone marrow aspirations, vital sign checks, questionnaires, and physical exams.

Conditions

Relapsed or Refractory Acute Leukemia; Relapsed or Refractory Acute Myeloid Leukemia

Keywords

NPM1c; KMT2At; NUP98t; AML; ALL; Acute Leukemia; Relapsed Refractory; S243249

Outcome Measures

Primary Outcomes (10)

• Incidence of Adverse Events (AEs)

  Through Safety Follow-up (Approximately 3 years)

• Severity of AEs

  Through Safety Follow-up (Approximately 3 years)

• Number of changes in laboratory values

  Through Safety Follow-up (Approximately 3 years)

• Number of changes in electrocardiogram (ECG)

  Through Safety Follow-up (Approximately 3 years)

• Number of changes in vital signs

  Through Safety Follow-up (Approximately 3 years)

• Number of AEs leading to dose interruption

  Through Safety Follow-up (Approximately 3 years)

• Number of AEs leading to dose modification

  Through Safety Follow-up (Approximately 3 years)

• Number of AEs leading to dose delays

  Through Safety Follow-up (Approximately 3 years)

• Number of AEs leading to permanent treatment discontinuation

  Through Safety Follow-up (Approximately 3 years)

• Complete remission (CR) + Complete remission with partial recovery of hematology (CRh) rate

  Through Long-term Follow-up (Approximately 5 years)

Secondary Outcomes (21)

• Overall response rate (ORR)

  Through Long-term Follow-up (Approximately 5 years)

• Composite complete remission (CRc) rate

  Through Long-term Follow-up (Approximately 5 years)

• CR rate

  Through Long-term Follow-up (Approximately 5 years)

• Rate of CR/CRh Minimal residual disease (MRD) negativity

  Through Long-term Follow-up (Approximately 5 years)

• Duration of response (DOR)

  Through Long-term Follow-up (Approximately 5 years)

Study Arms (4)

Phase 1 Dose Optimization: Cohort 1

EXPERIMENTAL

For participants without strong CYP3A4 inhibitors

Drug: S243249 600mg

Phase 1 Dose Optimization: Cohort 2

EXPERIMENTAL

For participants without strong CYP3A4 inhibitors

Drug: S243249 400mg

Phase 1 Dose Optimization: Cohort 3

EXPERIMENTAL

For participants with strong CYP3A4 inhibitors

Drug: S243249 450mg

Phase 1 Dose Optimization: Cohort 4

EXPERIMENTAL

For participants with strong CYP3A4 inhibitors

Drug: S243249 300mg

Interventions

S243249 600mg DRUG

Taken twice daily by mouth

Phase 1 Dose Optimization: Cohort 1

S243249 400mg DRUG

Taken twice daily by mouth

Phase 1 Dose Optimization: Cohort 2

S243249 300mg DRUG

Taken twice daily by mouth

Phase 1 Dose Optimization: Cohort 4

S243249 450mg DRUG

Taken twice daily by mouth

Phase 1 Dose Optimization: Cohort 3

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Aged ≥ 18 years old.
• Negative serum pregnancy (β-hCG) test in women of childbearing potential at screening
• Cytomorphology-confirmed diagnosis of R/R acute leukemia (including AML, ALL, and mixed lineage leukemia) according to the WHO criteria in 2022. R/R acute leukemia must meet at least one of the following conditions:
• Primary refractory disease, defined as non-response to 2 courses of standard induction therapy.
• R/R disease, defined as \> 5% blasts on bone marrow aspirate (BMA) / bone marrow biopsy (BMB) after completing prior therapy.
• Relapse after allogeneic hematopoietic stem cell transplantation (HSCT), autologous HSCT, or immunotherapy such as chimeric antigen receptor T cell therapy (CAR-T) and T cell engager (TCE).
• Participants with secondary AML or AML transformed from myelodysplastic syndrome (MDS), myeloproliferative neoplasm (MPN), etc., can be included in the study, if they meet the above criteria after the disease has transformed into AML.
• Confirmation of KMT2At, NUP98t, or NPM1c mutation using next generation sequencing (NGS), fluorescence in situ hybridization (FISH), or polymerase chain reaction (PCR) based test in an accredited local or central lab within 28 days before start of treatment.
• Peripheral blood white blood cell (WBC) count ≤ 25 mm3 (hydroxyurea, steroids, or vincristine to reduce peripheral WBC count is permitted).
• Participants will be at least 2 weeks from prior therapy (except hydroxyurea, vincristine, or steroids and prespecified prephase therapy) and recovered from nadir to no worse than Grade 1 nonhematological toxicity from the prior treatment.
• Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2.
• Adequate electrolytes, liver, kidney, and cardiac function
• Sexually active male or female participants of childbearing potential must agree to use 2 medically accepted forms of effective contraception, e.g., oral, parenteral, or implanted contraceptives; intrauterine devices; and barrier methods with spermicides, during the study and for 3 or 6 months after the final administration of investigational medicinal product (IMP), in males and females respectively. Egg donation is not allowed during the study or within 6 months of the last dose of S243249.
• Male participants with women of childbearing potential (WOCBP) partners must use a condom during the study and for at least 3 months after the final administration of IMP.

You may not qualify if:

• Active central nervous system (CNS) leukemia (including imaging abnormalities and cerebrospinal fluid (CSF) smear or flow cytometry indicating leukemia cells)).
• Active disseminated intravascular coagulation (DIC).
• Active uncontrolled infection (prophylaxis because of absolute neutrophil count \[ANC\] is excepted).
• Diagnosis of acute promyelocytic leukemia (APL, M3).
• Corrected QT interval calculated by Fridericia (QTcF) \> 450 msec on screening ECG.
• Participants with an increased pro-arrhythmic risk such as those with congenital long QT syndrome.
• Uncontrolled or severe cardiovascular disease, , within 12 months.
• Uncontrolled serious arrhythmias.
• Clinically significant pericardial disease.
• History of other malignancy within the past 5 years.
• Participants who receive autologous hematopoietic stem cell transplantation (ASCT) or CAR-T therapy within 60 days of the first dose of S243249 or have not yet recovered from toxicity related to ASCT or CAR-T therapy.
• Participants who receive allogeneic HSCT within 100 days of the first dose of S243249, still have active acute or chronic graft versus host disease (GVHD), or still require immune-modulating therapy.
• Have an active infection of hepatitis B or hepatitis C.
• Have advanced liver disease or cirrhosis.
• Uncontrolled human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome related illness.

Sponsors & Collaborators

• Servier: lead

MeSH Terms

Conditions

Recurrence; Leukemia, Myeloid, Acute

Condition Hierarchy (Ancestors)

Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Central Study Contacts

Institut de Recherches Internationales Servier (I.R.I.S.)

CONTACT

+33 1 55 72 60 00; scientificinformation@servier.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 13, 2026
• First Posted: July 23, 2026
• Study Start (Estimated): September 20, 2026
• Primary Completion (Estimated): August 11, 2029
• Study Completion (Estimated): August 25, 2030
• Last Updated: July 23, 2026

Record last verified: 2026-07

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: After Marketing Authorization in EEA or US if the study is used for the approval.
• Access Criteria: Researchers should register on Servier Data Portal and fill in the research proposal form. This form in four parts should be fully documented. The Research Proposal Form will not be reviewed until all mandatory fields are completed.