A Study to Evaluate S241656 Alone or in Combination in Participants With Selected Myeloid Malignancies

NCT07719348 | Not Yet Recruiting Phase 1 FDA Drug

• 2 other identifiers: S241656-2922025-525128-88-00
• Study Type: interventional
• Target: 64
• Locations: 0 countries
• Sites: N/A

Brief Summary

The objective of this study is to evaluate the safety, tolerability, and pharmacokinetics (PK) of S241656 and to determine the recommended dose for expansion (RDE) of S241656 in participants with relapsed/refractory (R/R) acute myeloid leukemia (AML), myelodysplastic syndrome/acute myeloid leukemia (MDS/AML), or chronic myelomonocytic leukemia (CMML). Part 1A dose escalation will determine the RDE to be used in a future expansion stage of the trial. An optional Part 1B drug-drug interaction (DDI) substudy will evaluate the effect of posaconazole on the PK of S241656. The study consists of a screening period of up to 21 days, a treatment period consisting of continuous 28-day cycles of treatment, an end-of-treatment visit, a safety follow-up period, and long-term disease and survival follow-up every 3 months. Participants in the optional DDI substudy may continue treatment in the main study following completion of the DDI assessment period. Participants may undergo bone marrow aspirates and/or biopsies, blood tests, electrocardiograms (ECGs), echocardiograms or multigated acquisition (MUGA) scans, physical examinations, ophthalmologic assessments, and disease response questionnaires.

Conditions

Acute Myeloid Leukemia; Chronic Myelomonocytic Leukemia; Myelodysplastic Syndrome Acute Myeloid Leukemia

Outcome Measures

Primary Outcomes (21)

• (Part 1A and 1B) Dose limiting toxicity (DLTs) associated with S241656 during the first cycle of treatment

  Through Cycle 1 (28 days)

• (Part 1A and 1B) Number of Adverse Events (AEs)

  Through 30 days after the last dose of treatment, up to approximately 4 years

• (Part 1A and 1B) Number of Serious Adverse Events (SAEs)

  Through 30 days after the last dose of treatment, up to approximately 4 years

• (Part 1A and 1B) Severity of AEs

  Through 30 days after the last dose of treatment, up to approximately 4 years

• (Part 1A and 1B) Severity of SAEs

  Through 30 days after the last dose of treatment, up to approximately 4 years

• (Part 1A and 1B) Duration of AEs

  Through 30 days after the last dose of treatment, up to approximately 4 years

• (Part 1A and 1B) Duration of SAEs

  Through 30 days after the last dose of treatment, up to approximately 4 years

• (Part 1A and 1B) Number of changes in safety laboratory results

  Through 30 days after the last dose of treatment, up to approximately 4 years

• (Part 1A and 1B) Number of changes in physical examination

  Through 30 days after the last dose of treatment, up to approximately 4 years

• (Part 1A and 1B) Number of dose reductions due to AEs

  Through end of treatment, up to approximately 4 years

• (Part 1A and 1B) Number of dose interruptions due to AEs

  Through end of treatment, up to approximately 4 years

• (Part 1A and 1B) Number of dose delays due to AEs

  Through end of treatment, up to approximately 4 years

• (Part 1A and 1B) Number of study withdrawals due to AEs

  Through end of treatment, up to approximately 4 years

• (Part 1B only) Maximum concentration (Cmax) of S241656

  Through Cycle 1 (28 days)

• (Part 1B only) Cmax of metabolite S243796

  Through Cycle 1 (28 days)

• (Part 1B only) Time corresponding to Cmax (Tmax) of S241656

  Through Cycle 1 (28 days)

• (Part 1B only) Tmax of metabolite S243796

  Through Cycle 1 (28 days)

• (Part 1B only) Terminal half-life (t1/2) of S241656

  Through Cycle 1 (28 days)

• (Part 1B only) t1/2 of metabolite S243796

  Through Cycle 1 (28 days)

• (Part 1B only) Area under the curve (AUC) of S241656

  Through Cycle 1 (28 days)

• (Part 1B only) AUC of metabolite S243796

  Through Cycle 1 (28 days)

Secondary Outcomes (22)

• (Part 1A only) Cmax of S241656

  Through end of treatment, up to approximately 4 years

• (Part 1A only) Cmax of metabolite S243796

  Through end of treatment, up to approximately 4 years

• (Part 1A only) Tmax of S241656

  Through end of treatment, up to approximately 4 years

• (Part 1A only) Tmax of metabolite S243796

  Through end of treatment, up to approximately 4 years

• (Part 1A only) AUC of S241656

  Through end of treatment, up to approximately 4 years

Study Arms (2)

Part 1A: Dose Escalation

EXPERIMENTAL

Drug: S241656

Part 1B: Optional Drug-Drug Interaction [DDI] Substudy

EXPERIMENTAL

Drug: S241656; Drug: Posaconazole

Interventions

S241656 DRUG

Tablets taken by mouth.

Part 1A: Dose Escalation; Part 1B: Optional Drug-Drug Interaction [DDI] Substudy

Posaconazole DRUG

Tablets taken by mouth

Part 1B: Optional Drug-Drug Interaction [DDI] Substudy

Eligibility Criteria

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

You may qualify if:

• Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 2.
• Investigator-assessed life expectancy of ≥ 3 months.
• Able and willing to comply with requirements of the study protocol.
• Documented genetic characterization of the disease as per local practice.
• Clinical and laboratory thresholds:
• Cytoreduction: white blood cell (WBC) \< 25 × 10⁹/L (hydroxyurea/cytarabine/leukapheresis allowed).
• Renal: creatinine clearance (CrCl) ≥ 60 mL/min (Cockcroft-Gault).
• Hepatic: aspartate aminotransferase (AST)/alanine aminotransferase (ALT) ≤ 3 × upper limit of normal (ULN) (5 × if leukemic); Total bilirubin ≤ 1.5 × ULN (≤ 3 × ULN for Gilbert's syndrome).
• Part 1 Only: Relapsed/Refractory (R/R), pathologically confirmed AML, MDS/AML, or CMML.
• Part 1 Only: Must have failed ≥ 1 approved standard therapy and have no other approved standard options.

You may not qualify if:

• Known hypersensitivity to S241656, or Posaconazole (Part 1B).
• Pregnant or breastfeeding; positive serum pregnancy test for WOCBP.
• Diagnosis of acute promyelocytic leukemia (French-American-British \[FAB\] M3 classification), MPN, mixed/ambiguous lineage, histiocytic/dendritic cell neoplasms, or AML with isolated extramedullary disease (no marrow/blood involvement).
• Active Central Nervous System (CNS) disease (by cytologic or radiographic evidence).
• Failure to recover to ≤ Grade 1 from previous toxicities (except Grade 2 neuropathy/alopecia).
• Major surgery within 4 weeks.
• Any anticancer therapy within 2 weeks or 5 half-lives (28 days for biologics). Cytoreduction with hydroxyurea or cytarabine is permitted.
• Prior use of experimental KRAS/BRAF/MEK/ERK inhibitors (prior FLT3 inhibitors are permitted).
• Uncontrolled infections (human immunodeficiency virus (HIV)/hepatitis B virus (HBV)/hepatitis C virus (HCV) permitted only if viral load is undetectable/controlled and specific cluster of differentiation 4 (CD4)+ criteria are met).
• Malabsorption, Crohn's, or chronic vomiting that impacts oral drug absorption.
• History/risk of retinal vein occlusion (RVO), glaucoma, or hyper-viscosity syndromes.
• Other active malignancy requiring systemic therapy within 2 years (except non-melanoma skin cancer or localized/cured tumors).
• Stroke, myocardial infarction (MI), unstable angina, or acute coronary syndrome within 6 months.
• Congestive heart failure (CHF), clinically significant cardiac arrhythmias according to the investigator's judgement (e.g., ventricular tachycardia), complete left bundle branch block and high-grade atrioventricular (AV) block (e.g., bifascicular block, Mobitz type II- and third degree AV block).
• Fridericia-corrected QT interval (QTcF) \> 470 msec or history of Torsades de pointes.

Sponsors & Collaborators

• Servier: lead

MeSH Terms

Conditions

Leukemia, Myeloid, Acute; Leukemia, Myelomonocytic, Chronic; GATA2 Deficiency

Interventions

posaconazole

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Myelodysplastic-Myeloproliferative Diseases; Bone Marrow Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Myelodysplastic Syndromes; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

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: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 8, 2026
• First Posted: July 22, 2026
• Study Start (Estimated): September 15, 2026
• Primary Completion (Estimated): November 1, 2027
• Study Completion (Estimated): September 30, 2030
• Last Updated: July 22, 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.