Investigating a new treatment for Acute Myeloid Leukemia using SAR443579 with other agents

A Phase 1/Phase 2, Randomized, Open-label, Multi Cohort, Multi Center, Study Assessing the Safety, Tolerability and Preliminary Efficacy of SAR443579 a Natural Killer Cell Engager (NKCE) Targeting CD123, Administered With Different Agents in Participants With CD123 Expressing Hematological Malignancies

This study is testing a new treatment called SAR443579 combined with other medications to see if it helps adults with newly diagnosed Acute Myeloid Leukemia feel better and improve their outcomes.

Quick facts

• Phase: PHASE1; PHASE2
• Study type: Interventional
• Enrollment: 18 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Sanofi (industry)
• Drugs / interventions: chemotherapy
• Locations: 7 sites (Duarte, California and 6 other locations)
• Trial ID: NCT06508489 on ClinicalTrials.gov

What this trial studies

This clinical trial is a Phase 1/Phase 2, open-label, multi-center study designed to assess the safety, tolerability, and preliminary efficacy of SAR443579 in combination with other agents, such as azacitidine and venetoclax, for treating adult participants with CD123 expressing hematological malignancies, specifically newly diagnosed Acute Myeloid Leukemia (ND-AML). The study will be conducted in three parts: dose finding, dose optimization, and dose expansion, allowing for a thorough evaluation of the treatment's effectiveness and safety. Participants will be monitored over approximately 2.5 years, including a follow-up period of up to 2 years after treatment.

Who should consider this trial

Good fit: Ideal candidates for this study are adults aged 18 years and older with newly diagnosed Acute Myeloid Leukemia who are ineligible for intensive chemotherapy.

Not a fit: Patients with hematological malignancies that do not express CD123 or those who are eligible for intensive chemotherapy may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a new therapeutic option for patients with Acute Myeloid Leukemia who are ineligible for intensive chemotherapy.

How similar studies have performed: Other studies have shown promise with similar approaches using combination therapies for hematological malignancies, indicating potential for success in this trial.

Eligibility criteria

Inclusion Criteria:

- 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:

1. Eastern Cooperative Oncology Group (ECOG) performance status 2-3.
2. 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.
3. Diffusing capacity of the lungs for carbon monoxide (DLCO) ≤65% or forced expiratory volume (FEV1) ≤65%.
4. Creatinine clearance ≥30 to \<45 mL/min calculated by modification of diet in renal disease (MDRD) formula.
5. 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)
* Subject with adequate liver function demonstrated by the following:

  1. For participants 18 to 74 years of age, aspartate aminotransferase (AST) ≤3.0 × ULN, alanine aminotransferase (ALT) ≤3.0 × ULN and bilirubin ≤3.0 × ULN, unless considered due to leukemic organ involvement ˂5 × ULN.
  2. For participants ≥75 years of age, aspartate aminotransferase (AST) ≤3.0 × ULN, alanine aminotransferase (ALT) ≤3.0 × ULN and bilirubin ≤1.5 × ULN, unless considered due to leukemic organ involvement ˂5 × ULN.

Exclusion Criteria:

* 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:

  1. 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.
  2. 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.
* Subject has received treatment with at least one of the following:

  1. A hypomethylating agent, venetoclax and/or chemo therapeutic agent for AML other than hydroxyurea used for disease control prior to the initiation of study therapy.
  2. Experimental therapies for AML.
  3. Concomitant medications of strong and moderate CYP3A inducers within 7 days prior to the initiation of study treatment.

The above information is not intended to contain all considerations relevant to a participant's potential participation in a clinical trial.

Where this trial is running

Duarte, California and 6 other locations

• City of Hope National Medical Center- Site Number : 8400003 — Duarte, California, United States (RECRUITING)
• Montefiore Medical Center- Site Number : 8400004 — Bronx, New York, United States (RECRUITING)
• The Ohio State University Wexner Medical Center - Ohio State Outpatient Care Upper Arlington- Site Number : 8400001 — Columbus, Ohio, United States (RECRUITING)
• Oregon Health and Science University- Site Number : 8400006 — Portland, Oregon, United States (RECRUITING)
• The University of Texas MD Anderson Cancer Center- Site Number : 8400008 — Houston, Texas, United States (RECRUITING)
• Investigational Site Number : 0360002 — Wollongong, New South Wales, Australia (RECRUITING)
• Investigational Site Number : 0360001 — Melbourne, Victoria, Australia (RECRUITING)

Study contacts

• Study coordinator: Trial Transparency email recommended (Toll free for US & Canada)

Conditions: Acute Myeloid Leukemia, AML