A Study to Investigate Natural Killer Cell Engager (SAR443579) With Different Agents in Participants With Hematological Malignancies

NCT06508489 | Terminated Phase 1 FDA Drug

• 3 other identifiers: TCD17796U1111-1280-61732023-509438-20
• Study Type: interventional
• Target: 7
• Locations: 2 countries
• Sites: 7

Brief Summary

This is a parallel, Phase 1/Phase 2, randomized, open label, multi-cohort, multi-center study assessing the safety, tolerability and preliminary efficacy of SAR443579 with different agents for treatment in adolescent and/or adult participants with CD123 expressing hematological malignancies. This protocol is structured as a master protocol (containing common protocol elements). Individual sub-studies will explore SAR443579 with combination partners, which may include approved or investigational agents. Experimental sub-studies will be tested through 3 parts: Part 1: dose finding (such as dose escalation/ safety run-in). Part 2: dose optimization (when applicable). Part 3: dose expansion. In each sub-study, a dose escalation will identify preliminary recommended dose for expansion (pRDE) of SAR443579 and its respective combination partner. Following the determination of the preliminary RDE, additional participants will be enrolled in the dose expansion part, or if dose optimization needs to be further evaluated, additional participants will be enrolled in the "dose optimization/expansion" part. Dose optimization and dose expansion part could involve randomization depending on specific sub-study design. Study will consist of a screening period, treatment period, and follow-up period. Participants will receive study treatment until documented disease progression, unacceptable adverse events, participant's decision to stop study treatment, or completion of the maximum cycles allowed in the sub-studies, or the participant meets other criteria for discontinuation per study protocol (whichever occurs first).

Conditions

Acute Myeloid Leukemia

Keywords

AML

Outcome Measures

Primary Outcomes (4)

• Number of participants with adverse events (AEs)/serious adverse events (SAEs)/adverse events of special interest (AESIs), laboratory abnormalities

  Day 1 to 30 days after the last administration of study treatment

• Substudy 01: Incidence of dose limiting toxicities (DLTs) (escalation part)

  Day 1 to Day 28

• Substudy 01: Complete Remission (CR) rate (optimization part)

  Proportion of participants who have a CR (Complete Remission) determined by the Investigator according to 2022 European Leukemia Net (ELN) recommendations for diagnosis and management of AML

  Day 1 to 30 days after the last administration of study treatment

• Substudy 01: Complete Remission (CR) rate (expansion part)

  Proportion of participants who have a CR (Complete Remission) determined by the Investigator according to 2022 European Leukemia Net (ELN) recommendations for diagnosis and management of AML

  Day 1 up to 6 months

Secondary Outcomes (21)

• Number of participants with treatment emergent adverse events (TEAEs), serious adverse events (SAEs), adverse events of special interest (AESIs) and clinically significant laboratory abnormalities (expansion part)

  Day 1 to 30 days after the last administration of study treatment

• Incidence of anti-drug anti body (ADA) against SAR443579

  Day 1 to 30 days after the last administration of study treatment

• Substudy 01: Percentage of participants with Minimal residual disease (expansion part)

  Day 1 up to 6 months

• Substudy 01: Pharmacokinetic (PK) parameter of SAR443579: Ctrough

  Day 1 up to 10 cycles (each cycle 28 days)

• Substudy 01: PK parameter of venetoclax: Cmax

  Day 1 to Day 28

Study Arms (1)

Substudy 01: SAR443579 + azacitidine + venetoclax

EXPERIMENTAL

Part 1: Safety run-in: SAR443579 treatment will begin with an identified starting dose. Safety run-in will proceed according to the incidence of DLTs.

Biological: SAR443579; Drug: venetoclax; Drug: azacitidine

Interventions

SAR443579 BIOLOGICAL

Pharmaceutical form: Powder for solution for infusion Route of administration: intravenous infusion

Substudy 01: SAR443579 + azacitidine + venetoclax

venetoclax DRUG

Pharmaceutical form :Film coated tablet Route of administration: oral

Also known as: VENCLYXTO / VENCLEXTA

Substudy 01: SAR443579 + azacitidine + venetoclax

azacitidine DRUG

Pharmaceutical form: Lyophilized powder for suspension for injection Route of administration: intravenous or subcutaneous

Substudy 01: SAR443579 + azacitidine + venetoclax

Eligibility Criteria

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

You may qualify if:

• \- Participants with CD123-expressing hematological neoplasm per the 5th edition of the WHO Classification of Hematolymphoid Tumors.
• Substudy 01:
• Participants must be ≥18 years of age
• Confirmed diagnosis of Acute Myeloid Leukemia
• Ineligible for intensive chemotherapy. Ineligible for intensive chemotherapy is defined by the following criteria:
• A) ≥ 75 years of age, OR
• B) 18 to 74 years of age and meeting one or more of the following:
• Eastern Cooperative Oncology Group (ECOG) performance status 2-3.
• Cardiac history of congestive heart failure (CHF) requiring treatment or left ventricular ejection fraction (LVEF) ≤50% or symptomatic coronary heart disease confirmed by coronarography or cardiac imaging.
• Diffusing capacity of the lungs for carbon monoxide (DLCO) ≤65% or forced expiratory volume (FEV1) ≤65%.
• Creatinine clearance ≥30 to \<45 mL/min calculated by modification of diet in renal disease (MDRD) formula.
• Moderate hepatic impairment with total bilirubin \>1.5 to ≤3.0x upper limit of normal (ULN).
• Subject with an Eastern Cooperative Oncology Group (ECOG) performance status as follows:
• a) 0 to 2 for participants ≥75 years of age or b) 0 to 3 for participants 18 to 74 years of age.
• For participants ≥75 years of age, adequate renal function demonstrated by a creatinine clearance ≥30 mL/min, calculated by modification of diet in renal disease (MDRD)

You may not qualify if:

• Any clinically significant, uncontrolled medical conditions (including any serious active systemic infection that is not controlled)
• Known second malignancy either progressing or requiring active treatment within the last 3 years prior to first IMP administration
• Known acquired immunodeficiency syndrome (AIDS-related illnesses) or HIV disease requiring antiretroviral treatment, or having active hepatitis B or C infection, or SARS-CoV-2 infection. With exception for:
• HBV as determined by positive test for hepatitis B surface antigen (HBsAg) and/or HBV DNA. Participant who tests positive for anti-hepatitis B core (HBc) antigen IgG (with or without testing positive for anti-HBs), but tests negative for HBsAg and HBV DNA, is eligible.
• A participant who tests positive for anti-HCV antibodies and has undetectable HCV RNA without receiving antiviral treatment for HCV is eligible.
• Active, known, or suspected clinically significant autoimmune disease that has required systemic treatment in the past 2 years prior to first IMP administration, except controlled by replacement therapy (eg, thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc)
• Predicted life expectancy ≤3 months.
• Medical conditions requiring treatment with medications with narrow therapeutic index that are substrates of CYP enzymes and that cannot be closely monitored to allow for dose adjustment.
• Ongoing adverse event of NCI CTCAE \[Version 5.0\] Grade 2 or greater severity cause by any prior anti-cancer therapy
• Substudy 01:
• Patient with Acute Promyelocytic Leukemia (APL)
• Known active central nervous system involvement with AML at the time of enrollment as evidenced by cytology or pathology
• Cardiovascular disease of New York Heart Association (NYHA) Class ≥2.
• Malabsorption syndrome or other condition that precludes enteral route of administration
• A baseline QTc interval of (using the Fridericia correction calculation) \>470 msec.

Sponsors & Collaborators

• Sanofi: lead

Study Sites (7)

City of Hope National Medical Center- Site Number : 8400003

Duarte, California, 91010, United States

Location

Montefiore Medical Center - Moses Campus- Site Number : 8400004

The Bronx, New York, 10467, United States

Location

The Ohio State University Wexner Medical Center - Ohio State Outpatient Care Upper Arlington- Site Number : 8400001

Columbus, Ohio, 43221, United States

Location

Oregon Health and Science University- Site Number : 8400006

Portland, Oregon, 97239, United States

Location

The University of Texas MD Anderson Cancer Center- Site Number : 8400008

Houston, Texas, 77030, United States

Location

Investigational Site Number : 0360002

Wollongong, New South Wales, 2500, Australia

Location

Investigational Site Number : 0360001

Melbourne, Victoria, 3000, Australia

Location

MeSH Terms

Conditions

Leukemia, Myeloid, Acute

Interventions

venetoclax; Azacitidine

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Aza Compounds; Organic Chemicals; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides

Study Design

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

Study Record Dates

• First Submitted: June 27, 2024
• First Posted: July 18, 2024
• Study Start: August 13, 2024
• Primary Completion: August 8, 2025
• Study Completion: August 8, 2025
• Last Updated: August 22, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will share

Locations

AU (2); US (5)