Relapsed or Refractory Acute LeukemiaPhase 1/2NCT07722312
S243249 Monotherapy in Patients With Relapsed or Refractory Acute Leukemia With a KMT2A or NUP98 Translocation or Relapsed or Refractory AML With NPM1c Mutation
A Phase 1/2 study testing S243249 600mg, S243249 400mg and S243249 450mg in people with Relapsed or Refractory Acute Leukemia and Relapsed or Refractory Acute Myeloid Leukemia, run by Servier.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Relapsed or Refractory Acute Leukemia, Relapsed or Refractory Acute Myeloid Leukemia
- What is being tested?
- S243249 600mg, S243249 400mg and S243249 450mg
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 80 participants
- Where
- No sites listed yet
- Study dates
- 20 Oct 2026to 25 Aug 2030
- Phase
- Phase 1/2
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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).
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- 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.
Who cannot join
- 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.
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- 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.
- Pregnant and/or breast-feeding (lactating) women.
- Participant has received anti-leukemia treatment, including chemotherapy, radiation therapy, targeted small molecule agents, biologic agents, immunotherapy, or any other investigational therapy (excluding hydroxyurea, or vincristine for cytoreduction) within 2 weeks prior to the first dose of S243249.
- Previous treatment targeting menin, dose optimization phase only.
- Any concomitant participation in another therapeutic clinical trial is prohibited. Any participation in another nontherapeutic clinical trial could be approved by the medical monitor.
- Participants taking medications known to prolong the QT/QTc interval (with the exception of necessary azole antifungals).
- Ongoing toxicity from prior anti-leukemia therapy that has not resolved to Grade 1 7 days prior to the first dose of S243249 has to be approved by the medical monitor.
- Uncontrolled active infection
- Known allergy or hypersensitivity to menin inhibitors or any component of S243249.
Trial locations and contacts
No sites are listed yet. Contact the study team or a site near you to ask about taking part.
Institut de Recherches Internationales Servier (I.R.I.S.) contact
About this study
Official title: A Phase 1/2, Dose Optimization and Dose Expansion, Multicenter, Open-label Study to Evaluate the Safety, Pharmacokinetics, and Efficacy of Menin Inhibitor S243249 Monotherapy in Patients With Relapsed or Refractory Acute Leukemia With a KMT2A or NUP98 Translocation or Patients With Relapsed or Refractory Acute Myeloid Leukemia With NPM1c Mutation
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.
- Being tested
- S243249 600mg, S243249 400mg, S243249 450mg, S243249 300mg
- Keywords
- NPM1c, KMT2At, NUP98t, AML, ALL, Acute Leukemia, Relapsed Refractory, S243249
- Medical subject headings
- Recurrence, Leukemia, Myeloid, Acute
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
S243249 600mgDrug
Taken twice daily by mouth
S243249 400mgDrug
Taken twice daily by mouth
S243249 450mgDrug
Taken twice daily by mouth
S243249 300mgDrug
Taken twice daily by mouth
| Study group | Role | What they receive |
|---|---|---|
| Phase 1 Dose Optimization: Cohort 1 | Experimental | For participants without strong CYP3A4 inhibitors Receives: Drug: S243249 600mg |
| Phase 1 Dose Optimization: Cohort 2 | Experimental | For participants without strong CYP3A4 inhibitors Receives: Drug: S243249 400mg |
| Phase 1 Dose Optimization: Cohort 3 | Experimental | For participants with strong CYP3A4 inhibitors Receives: Drug: S243249 450mg |
| Phase 1 Dose Optimization: Cohort 4 | Experimental | For participants with strong CYP3A4 inhibitors Receives: Drug: S243249 300mg |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence of Adverse Events (AEs)
Measured: Through Safety Follow-up (Approximately 3 years)
Severity of AEs
Measured: Through Safety Follow-up (Approximately 3 years)
Number of changes in laboratory values
Measured: Through Safety Follow-up (Approximately 3 years)
Number of changes in electrocardiogram (ECG)
Measured: Through Safety Follow-up (Approximately 3 years)
Number of changes in vital signs
Measured: Through Safety Follow-up (Approximately 3 years)
Number of AEs leading to dose interruption
Measured: Through Safety Follow-up (Approximately 3 years)
Number of AEs leading to dose modification
Measured: Through Safety Follow-up (Approximately 3 years)
Number of AEs leading to dose delays
Measured: Through Safety Follow-up (Approximately 3 years)
Number of AEs leading to permanent treatment discontinuation
Measured: Through Safety Follow-up (Approximately 3 years)
Complete remission (CR) + Complete remission with partial recovery of hematology (CRh) rate
Measured: Through Long-term Follow-up (Approximately 5 years)
Secondary outcomes (21)
Overall response rate (ORR)
CR + CRh + Complete remission with incomplete hematological recovery (CRi) + Morphologically leukemic state (MLFS) + Partial remission (PR)
Measured: Through Long-term Follow-up (Approximately 5 years)
Composite complete remission (CRc) rate
CRc is CR + CRh + CRi
Measured: Through Long-term Follow-up (Approximately 5 years)
CR rate
Measured: Through Long-term Follow-up (Approximately 5 years)
Rate of CR/CRh Minimal residual disease (MRD) negativity
Measured: Through Long-term Follow-up (Approximately 5 years)
Duration of response (DOR)
Measured from the date of first achievement of CR/CRh, CR, CR/CRh MRD negativity, CRc and ORR until hematologic relapse or death from any cause
Measured: Through Long-term Follow-up (Approximately 5 years)
Time to response (TTR)
Measured from the date of first dose administration until the first achievement of CR/CRh, CR, CR/CRh MRD negativity, CRc and ORR
Measured: Through Long-term Follow-up (Approximately 5 years)
Transfusion independence 56 days (TI-56)
The absence of red blood cells and platelet transfusions lasting for 56 consecutive days during which the patient is either on Investigational medicinal product (IMP) or following discontinuation from IMP but before the start of new therapy.
Measured: Through Long-term Follow-up (Approximately 5 years)
Transfusion independence 112 days (TI-112)
The absence of red blood cells and platelet transfusions lasting for 112 consecutive days during which the patient is either on IMP or following discontinuation from IMP but before the start of new therapy.
Measured: Through Long-term Follow-up (Approximately 5 years)
Event free survival (EFS)
Measured: Through Long-term Follow-up (Approximately 5 years)
Cumulative relapse rate (CIR)
Measured: Through Long-term Follow-up (Approximately 5 years)
Cumulative mortality (CID)
Measured: Through Long-term Follow-up (Approximately 5 years)
Overall survival (OS)
Measured: Through Long-term Follow-up (Approximately 5 years)
Quality of Life (QoL) measured via EuroQol 5-Dimension 5-Level questionnaire (EQ-5D-5L)
EQ-5D-5L scores range from 0-5 with 5 representing the best QoL.
Measured: Through Safety Follow-up (Approximately 3 years)
QoL measured via Hematological malignancy specific patient-reported outcome (HM-PRO)
HM-PRO Part A scores range from 0 to 48 and Part B scores from 0 to 36, with a higher score representing the largest impact on quality of life.
Measured: Through Safety Follow-up (Approximately 3 years)
Health economic outcomes measured via EQ-5D-5L
EQ-5D-5L scores range from 0-1 with 1 representing the best health economic outcomes.
Measured: Through Safety Follow-up (Approximately 3 years)
Health economic outcomes measured via HM-PRO
HM-PRO scores range from 0 to 48, with a higher score representing the largest impact on health economic outcomes.
Measured: Through Safety Follow-up (Approximately 3 years)
Ability to proceed to hematopoietic stem cell transplantation (HSCT) as assessed by the investigator
Measured: Through Long-term Follow-up (Approximately 5 years)
Plasma concentration of S243249 and relevant metabolites
Plasma samples will be analyzed to determine concentrations of S243249 and relevant metabolites
Measured: Through Cycle 6 Day 1 (each cycle is 28 days)
Tmax
Time to observed maximum plasma concentration of S243249 and relevant metabolites
Measured: Through Cycle 6 Day 1 (each cycle is 28 days)
Cmax
Maximum plasma concentration of S243249 and relevant metabolites
Measured: Through Cycle 6 Day 1 (each cycle is 28 days)
AUC0-t
Area under the plasma concentration-time curve from time 0 to time t of S243249 and relevant metabolites
Measured: Through Cycle 6 Day 1 (each cycle is 28 days)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Jul 2026
- Study start20 Oct 2026 (estimated)
- Primary completion11 Aug 2029 (estimated)
- Study completion25 Aug 2030 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Relapsed or Refractory Acute LeukemiaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 80 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Servier
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07722312
- Sponsor's protocol ID
- BN104-102
- Other IDs
- 2025-524689-74-00, 2025
- Status last verified
- Sep 2026
- First submitted
- 13 Jul 2026
- Last updated
- 3 Sep 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: Qualified scientific and medical researchers can request access to anonymized patient-level and study-level clinical trial data. Access can be requested for all interventional clinical studies: * used for Marketing Authorization (MA) of medicines and new indications approved after 1 January 2014 in the European Economic Area (EEA) or the United States (US). * where Servier is the Marketing Authorization Holder (MAH). The date of the first MA of the new medicine (or the new indication) in one of the EEA Member States will be considered for this scope. In addition, access can be requested for all interventional clinical studies in patients: * sponsored by Servier * with a first patient enrolled as of 1 January 2004 onwards for New Chemical Entity or New Biological Entity (new pharmaceutical form excluded) for which development has been terminated before any Marketing authorization (MA) approval.