A Study to Evaluate S227928 as a Single Agent and in Combination With Venetoclax in Patients With R/R AML, MDS/AML, or CMML

NCT06563804 | Terminated Phase 1 FDA Drug

• 1 other identifier: S227928-180
• Study Type: interventional
• Target: 13
• Locations: 6 countries
• Sites: 16

Brief Summary

The objective of this study is to determine the safety, tolerability, and anti-leukemic activity of S227928 as single agent and in combination with venetoclax, and to determine the recommended Phase 2 dose (RP2D) of this combination. The study will begin as a Phase 1 Dose Escalation study to determine the RP2D and then will transition to a Phase 2 Dose Expansion study to assess the efficacy of the selected RP2D. During the treatment period participants will have study visits every two weeks, with additional visits occurring during the first and second cycle. Approximately 30 days after treatment has ended, an end-of-treatment visit will occur and then participants will be followed for survival every 12 weeks for the next 6 months. Study visits may include a bone marrow aspirate and/or biopsy, blood and urine tests, ECG, vital signs, physical examination, and administration of study treatment.

Conditions

Relapsed/Refractory (R/R) Acute Myeloid Leukemia (AML); Myelodysplastic Syndrome (MDS)/AML; Chronic Myelomonocytic Leukemia (CMML)

Outcome Measures

Primary Outcomes (4)

• Dose Escalation: Number and severity of Dose Limiting Toxicities (DLTs)

  Through Cycle 1 (each cycle is 28 days)

• Dose Escalation: Number of Adverse Events (AEs) and Serious Adverse Events (SAEs)

  Through 30 days after the end of treatment (Approximately 3.5 years)

• Dose Escalation: Number of dose reductions, interruptions, delays, or study withdrawal due to AEs

  Through 30 days after the end of treatment (Approximately 3.5 years)

• Dose Expansion: Complete remission (CR)

  Through 6 months after the end of treatment (Approximately 4 years)

Secondary Outcomes (48)

• Dose Escalation: Cmax of S227928, total Monoclonal Antibody (mAb), and unconjugated S64315

  Through the end of treatment (Approximately 3.5 years)

• Dose Expansion: Cmax of S227928, total mAb, and unconjugated S64315

  Through the end of treatment (Approximately 3.5 years)

• Dose Escalation: Tmax of S227928, total mAb, and unconjugated S64315

  Through the end of treatment (Approximately 3.5 years)

• Dose Expansion: Tmax of S227928, total mAb, and unconjugated S64315

  Through the end of treatment (Approximately 3.5 years)

• Dose Escalation: Area Under the Curve (AUC) of S227928, total mAb, and unconjugated S64315

  Through the end of treatment (Approximately 3.5 years)

Study Arms (4)

Dose Escalation - Arm A

EXPERIMENTAL

S227928 as a single agent

Drug: S227928

Dose Escalation - Arm B

EXPERIMENTAL

S227928 in combination with venetoclax

Drug: S227928; Drug: Venetoclax

Dose Expansion - Cohort 1

EXPERIMENTAL

For participants with R/R AML and MDS/AML. S227928 in combination with venetoclax at RP2D

Drug: S227928; Drug: Venetoclax

Dose Expansion - Cohort 2

EXPERIMENTAL

For participants with CMML. S227928 in combination with venetoclax at RP2D

Drug: S227928; Drug: Venetoclax

Interventions

Venetoclax DRUG

For oral administration

Dose Escalation - Arm B; Dose Expansion - Cohort 1; Dose Expansion - Cohort 2

S227928 DRUG

For administration via intravenous (IV) infusion

Dose Escalation - Arm A; Dose Escalation - Arm B; Dose Expansion - Cohort 1; Dose Expansion - Cohort 2

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 ≤ 2
• Women of childbearing potential (WOCBP) must use a highly effective method of birth control during study treatment and at least 6 months after the last dose of Investigational Medicinal Product (IMP). In case of the use of oral contraception, women should have been on a stable dose of the same contraceptive drug (i.e., same active principle) for at least 3 months prior to the first IMP administration.
• Male participants with WOCBP partners must use a condom during the study and for at least 3 months after the last dose of IMP. In addition, contraception should be considered for their female partners. Contraceptive measures do not apply if the participant is sterile, vasectomised or sexually abstinent. Sperm donation will not be allowed during the study and for at least 3 months after the last dose of IMP.
• Patients with pathologically confirmed AML, MDS/AML, or CMML as defined by the World Health Organization (WHO) 2022 classification or ICC, who have been previously treated with at least one prior standard treatment and have relapsed and/or refractory disease.
• Patients must not be candidates for further standard therapy,
• Treatment with agents for lower risk MDS such as erythropoietin or luspatercept are not considered anticancer therapies.
• Adequate renal function within 7 days before study enrollment defined as:
• a. Calculated creatinine clearance (determined by the modification of diet in renal disease \[MDRD\] equation) ≥ 60 mL/min
• Adequate hepatic function within 7 days before study enrollment defined as:
• Aspartate aminotransferase (AST) and Alanine aminotransferase (ALT) ≤ 3 x upper limit of normal (ULN),
• Total bilirubin level ≤ 1.5 x ULN, except for patients with known Gilbert's syndrome, who may be included if their total bilirubin is ≤ 3.0 x ULN and their direct bilirubin is ≤ 1.5 x ULN.

You may not qualify if:

• Pregnant or lactating women.
• WOCBP tested positive in a serum pregnancy test within 7 days prior to the first day of IMP administration.
• Legally incapacitated person under guardianship or trusteeship.
• Failure to recover to ≤ Grade 1 (Common Terminology Criteria for Adverse Events version 5.0 \[CTCAE v5.0\]) from acute non-hematologic toxicities (to ≤ Grade 2 for neuropathy) due to previous therapy, prior to screening.
• Diagnosis of myeloproliferative neoplasms (MPNs) or other non-CMML MDS/MPNs as defined by the WHO 2022 classification
• Diagnosis of acute promyelocytic leukemia (French-American-British \[FAB\] M3 classification).
• Diagnosis of acute leukemia of mixed or ambiguous lineage or histiocytic/dendritic cell neoplasms defined by the WHO 2022 classification
• Uncontrolled infections requiring systemic antibiotics and/or antifungal agents as per investigator's judgment. Patients receiving prophylactic antibiotics and/or antifungal agents are eligible for this study.
• Serologic evidence of chronic hepatitis B virus (HBV) infection and unable or unwilling to receive standard prophylactic antiviral therapy, or with detectable HBV viral load.
• Serologic evidence of hepatitis C virus (HCV) infection without completion of curative treatment or with detectable HCV viral load.
• Human immunodeficiency virus (HIV) seropositive with any of the following:
• CD4+ T-cell (CD4+) counts \< 350 cells/µL
• Acquired immunodeficiency syndrome-defining opportunistic infection within 12 months prior to screening
• Not on antiretroviral therapy, or on antiretroviral therapy for \< 6 weeks at the time of Day 1 in Cycle 1
• HIV viral load ≥ 400 copies/mL

Sponsors & Collaborators

• Servier Bio-Innovation LLC: lead

Study Sites (16)

City of Hope

Duarte, California, 91010, United States

Location

The University of Kansas

Fairway, Kansas, 66205, United States

Location

START Midwest

Grand Rapids, Michigan, 49546, United States

Location

Memorial Sloan Kettering

New York, New York, 10065, United States

Location

Fred Hutch Cancer Center

Seattle, Washington, 98109, United States

Location

Peter MacCallum Cancer Centre

Melbourne, 3000, Australia

Location

Prince of Wales Hospital

Randwick, 2031, Australia

Location

Helsinki University Hospital - Comprehensive Cancer Center

Helsinki, 00029, Finland

Location

Institut Paoli Calmette

Marseille, 13009, France

Location

Chu de Nice - Hôpital L'archet 1

Nice, 062000, France

Location

CHU de Bordeaux - Hopital du Haut Levêque

Pessac, 33604, France

Location

Institut Gustave Roussy

Villejuif, 94800, France

Location

Klinikum rechts der Isar der TU München

München, 81675, Germany

Location

Universitätsklinikum Ulm

Ulm, 89081, Germany

Location

Sapporo Hokuyu Hospital

Hokkaido, 003-0006, Japan

Location

Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital

Tokyo, 113-8677, Japan

Location

MeSH Terms

Conditions

Recurrence; Leukemia, Myeloid, Acute; Myelodysplastic Syndromes; Leukemia, Myelomonocytic, Chronic

Interventions

venetoclax

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; Bone Marrow Diseases; Myelodysplastic-Myeloproliferative Diseases; Chronic Disease

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: August 14, 2024
• First Posted: August 21, 2024
• Study Start: February 25, 2025
• Primary Completion: October 9, 2025
• Study Completion: October 9, 2025
• Last Updated: March 30, 2026

Record last verified: 2026-03

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.

Locations

JP (2); FI (1); FR (4); DE (2); US (5); AU (2)