First-in-human Study of SAR443579 Infusion in Male and Female Children and Adult Participants With Relapsed or Refractory Acute Myeloid Leukemia (R/R AML), B-cell Acute Lymphoblastic Leukemia (B-ALL), High Risk-myelodysplasia (HR-MDS), or Blastic Plasmacytoid Dendritic Cell Neoplasm (BPDCN)

NCT05086315 | Terminated Phase 1 Results FDA Drug

• 4 other identifiers: TCD17197U1111-1266-73992023-508357-582021-004287-98
• Study Type: interventional
• Target: 101
• Locations: 5 countries
• Sites: 23

Brief Summary

This is an open-label, multicenter, Phase 1/Phase 2, dose escalation and dose expansion study to evaluate the safety, pharmacokinetics, pharmacodynamics and anti-leukemic activity of SAR443579 in various hematological malignancies.

Conditions

Acute Myeloid Leukaemia Refractory; Myelodysplastic Syndromes; Blastic Plasmacytoid Dendritic Cell Neoplasia; Acute Lymphocytic Leukaemia

Outcome Measures

Primary Outcomes (4)

• Dose Escalation: Number of Participants With Dose Limiting Toxicities (DLTs)

  The DLT was defined as any of the following events during Cycle 1 (first 28 days) using NCI CTCAE v5.0 or ASTCT criteria, whether related or not to the study treatment in the absence of clear evidence to the contrary, and if not related to disease progression. Hematologic DLTs included hematologic toxicities, bone marrow hypocellularity, decreased neutrophils lasting, febrile neutropenia, decreased platelet count lasting, anemia (all Grade 4), and Grade 3 thrombocytopenia. Non-hematologic DLTs included any Grade \>=3 toxicities except alopecia, Grade 3 fatigue, asthenia, fever, anorexia, constipation, nausea, vomiting, diarrhea, total parenteral nutrition, hospitalization related events, infection, bleeding, Grade 3 infusion related reaction and laboratory abnormalities, Grade 3 or 4 tumor lysis syndrome and isolated electrolyte abnormalities. Also, DLTs were any treatment related toxicity causing \>2 week delay in recovery to baseline/Grade \<=1 or requiring dose reduction.

  Cycle 1 Day 1 up to Cycle 1 Day 28. Each cycle duration in induction period was 28 days.

• Dose Escalation (Cohort C): Number of Participants With Dose Limiting Toxicities

  The DLT was defined as any of the following events during Cycle 1 (first 28 days) using NCI CTCAE v5.0 or ASTCT criteria, whether related or not to the study treatment in the absence of clear evidence to the contrary, and if not related to disease progression. Hematologic DLTs included hematologic toxicities, bone marrow hypocellularity, decreased neutrophils lasting, febrile neutropenia, decreased platelet count lasting, anemia (all Grade 4), and Grade 3 thrombocytopenia. Non-hematologic DLTs included any Grade \>=3 toxicities except alopecia, Grade 3 fatigue, asthenia, fever, anorexia, constipation, nausea, vomiting, diarrhea, total parenteral nutrition, hospitalization related events, infection, bleeding, Grade 3 infusion related reaction and laboratory abnormalities, Grade 3 or 4 tumor lysis syndrome and isolated electrolyte abnormalities. Also, DLTs were any treatment related toxicity causing \>2 week delay in recovery to baseline/Grade \<=1 or requiring dose reduction.

  Cycle 1 Day 1 to Cycle 1 Day 28. Each cycle duration in induction period was 28 days.

• Dose Expansion (Cohorts A1, A2 and D): Composite Complete Remission (CRc) Rate

  The CRc rate was defined as the percentage of participants who had a response of complete remission (CR), CR with partial hematologic recovery (CRh) or CR with incomplete hematologic recovery (CRi) according to modified AML International Working Group (IWG) 2003 response criteria.

  Tumors were assessed on Day 28 of each induction cycle and Day 56 of each maintenance cycle until disease relapse, unacceptable AE, discontinuation, or death, whichever occurred first. Maximum treatment duration was 20.9 weeks.

• Dose Expansion (Cohort B): Overall Response Rate (ORR)

  The ORR was defined as the percentage of participants who had a response of CR, CR equivalent, partial remission (PR), CR with limited count recovery (CRL), CRh or hematologic improvement (HI) according to IWG 2023 myelodysplastic syndrome (MDS) response criteria.

  Tumors were planned to assess on Day 28 of each induction cycle and Day 56 of each maintenance cycle until disease relapse, unacceptable AE, discontinuation, or death, whichever occurred first.

Secondary Outcomes (18)

• Dose Expansion (Cohorts A1, A2, B and D): Recommended Dose for Expansion (RDE)

  Cycle 1 Day 1 up to Cycle 1 Day 28. Each cycle duration in induction period was 28 days.

• Dose Escalation and Dose Expansion (Cohort A1): Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (SAEs)

  From the first dose of study drug administration (Day 1) up to early termination of the study, maximum treatment duration was 117.3 weeks for dose escalation (adult), 12 weeks for dose escalation (pediatric) and 20.9 for dose expansion (Cohort A1).

• Dose Escalation and Dose Expansion (Cohort A1): Minimum Plasma Concentration (Ctrough) of SAR443579

  At Days 1, 4, 8, 11, 15, 22, and 28 of Cycle 1

• Dose Escalation and Dose Expansion (Cohort A1): Percentage of Participants With Anti-drug Antibodies (ADA) Against SAR443579

  From the first dose of study drug administration (Day 1) up to early termination of the study, maximum treatment duration was 117.3 weeks for dose escalation (adult), 12 weeks for dose escalation (pediatric) and 20.9 for dose expansion (Cohort A1).

• Dose Escalation and Dose Expansion (Cohort C): Composite Complete Remission Rate Assessed by Acute Myeloid Leukemia 2003 Modified International Working Group Response Criteria and National Comprehensive Cancer Network (NCCN)

  Tumors were assessed on Day 28 of each induction cycle and Day 56 of each maintenance cycle until relapse, unacceptable AE, discontinuation or death. Maximum treatment duration: 117.3 weeks (adults) and 12 weeks (pediatrics) in dose escalation phase.

Study Arms (1)

SAR443579

EXPERIMENTAL

Dose Escalation: SAR443579 administered intravenously at escalating dose levels. Dose Expansion: SAR443579 administered intravenously at the recommended dose and schedule determined from the dose escalation.

Drug: SAR443579

Interventions

SAR443579 DRUG

Powder for solution for infusion; by IV infusion

SAR443579

Eligibility Criteria

• Age: 1 Year+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Participant must be at least 1 year (for France: 2 years) old at the time the trial participant or legal guardian signs the informed consent form and will be assigned as follows:
• Adult arm: aged at least 18 years old.
• Pediatric arm: aged 1 (for France: 2 years) to less than 18 years old.
• Adult and Pediatric Arms: Escalation and Expansion/Optimization Cohorts A1, A2, C, D: Confirmed diagnosis of primary or secondary AML (any subtype) according to World Health Organization (WHO) 2022 classification. Participants with AML must meet one of the following criteria, a), b), c) or d) and are limited to those with no available (or are ineligible) therapy with known clinical benefit.
• a) Primary Induction Failure (PIF) AML, defined as disease refractory to one of the following, i or ii.
• i) An intensive induction attempt, per institution. Induction attempts include high-dose and/or standard-dose cytarabine ± an anthracyclines/anthracenedione ± an anti-metabolite, with or without growth factor or targeted therapy containing regimens.
• ii) For adults who are age 75 years or older, or who have comorbidities that preclude use of intensive induction chemotherapy; PIF is defined as AML refractory to one of the following less intensive regimens, 1 or 2:
• cycles of hypomethylating agents (HMA) or
• cycles HMA + venetoclax b) Early relapse (ER) AML, defined as AML in relapse with CR, CRh or CRi duration less than 6 months on prior induction treatment c) Leukemia in first or higher relapse d) For participants aged 1 (for France: 2 years) to less than 18 years old, primary induction failure is defined as disease refractory after two cycles of induction therapy.
• Adult Arm (Escalation and Expansion/Optimization Cohorts B and Japan Cohort C only): Confirmed diagnosis of MDS, meeting the following criteria:
• intermediate or high-risk category as per a Revised International Prognostic Scoring System (IPSS-R) AND
• confirmed CD123 + expression status determined by local institutional standards AND
• limited to those with no available (or are ineligible) therapy with known clinical benefit.
• Pediatric arms escalation part and Japan Cohort C only: Confirmed diagnosis of CD123+ BALL without extramedullary lesions that have no available (or are ineligible) therapy with known clinical benefit. Participants with non-CNS chloromatous disease are not allowed in the study.
• Body weight at least 10 kg.

You may not qualify if:

• Eastern Cooperative Oncology Group (ECOG) performance status greater than 2 (at least 18 years-old). Karnofsky Scale (16 to 17 years-old) less than 50% or Lansky Scale (less than 16 years-old) less than 50%.
• History of an invasive malignancy within the last 3 years prior to first IMP administration that requires active therapy (adjuvant hormonal therapy is allowed) other than the one treated in this study.
• Evidence of active central nervous system leukemia at the time of enrollment as evidenced by cytology or pathology. Except for participants aged 1 (for France: 2 years) to less than 18 years, central nervous system 1 disease (CNS1) and CNS2 disease are allowed.
• Known acquired immunodeficiency syndrome (AIDS-related illnesses) or human immunodeficiency virus (HIV) disease requiring antiretroviral treatment, or having active hepatitis B or C infection, or severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection.
• Prior treatment with an anti-CD123-directed agent (except for participants with BPDCN in the pediatric arm).
• Prior HSCT with relapse beyond 3 months or prior CAR-T therapy in B-ALL with relapse beyond 2 months may be included only if off immunosuppression for a minimum of 4 weeks and no evidence of GVHD.
• Receiving at the time of first investigational medicinal product (IMP) administration corticosteroid as a concomitant medication with corticosteroid dose more than 10 mg/day of oral prednisone or the equivalent.
• AML, BPDCN, or HR-MDS participants with prior treatment with cellular therapy, eg, chimeric antigen receptor T cell (CAR-T) or chimeric antigen receptor NK cell (CAR-NK). Prior CAR-T therapy is allowed for participants with B-ALL.
• Concurrent treatment with other investigational drugs.
• Pregnant and breast-feeding women.
• History of solid organ transplant, including corneal transplant.
• Average QTc (using the Fridericia correction calculation) greater than 470 millisecond (msec) at screening.
• Pediatric arm only: Participants with known inherited bone marrow failure syndromes (e.g., bloom syndrome, ataxia-telangiectasia, Fanconi anemia, Kostmann syndrome, Shwachman syndrome). Participants with Down syndrome with adequate organ function as per Investigator discretion are allowed to participate in the study.
• Adult arm Expansion/Optimization- Participants with MDS evolving from a pre-existing myeloproliferative neoplasm (MPN), MDS/MPN including chronic myelomonocytic leukemia (CMML), atypical chronic myeloid leukemia (aCML), unclassifiable MDS/MPN and therapy-related MDS (t-MDS).
• Confirmed diagnosis of acute promyelocytic leukemia (APL) or juvenile myelomonocytic leukemia (JMML) according to WHO 2022 classification.

Sponsors & Collaborators

• Sanofi: lead

Study Sites (23)

City of Hope-Site Number:8400002

Duarte, California, 91010, United States

Location

Emory University School of Medicine- Grady Campus- Site Number : 8400006

Atlanta, Georgia, 30303, United States

Location

Beth Israel Deaconess Medical Center-Site Number:8400004

Boston, Massachusetts, 02215, United States

Location

Weill Cornell Medical College-Site Number:8400003

New York, New York, 10021, United States

Location

Montefiore Hutchinson Campus- Site Number : 8400012

The Bronx, New York, 10461, United States

Location

The Ohio State University- Site Number : 8400009

Columbus, Ohio, 43210, United States

Location

Oregon Health and Science University-Site Number:8400011

Portland, Oregon, 97239, United States

Location

The Children's Hospital of Philadelphia- Site Number : 8400013

Philadelphia, Pennsylvania, 19104, United States

Location

MD Anderson Cancer Center-Site Number:8400001

Houston, Texas, 77030, United States

Location

Seattle Children's Hospital- Site Number : 8400014

Seattle, Washington, 98105, United States

Location

Investigational Site Number :0360002

Melbourne, Victoria, 3000, Australia

Location

Investigational Site Number :0360001

Melbourne, Victoria, 3004, Australia

Location

Investigational Site Number : 1560001

Tianjin, 300020, China

Location

Investigational Site Number : 1560003

Zhengzhou, 450008, China

Location

Investigational Site Number :2500002

Marseille, 13009, France

Location

Investigational Site Number :2500001

Paris, 75010, France

Location

Investigational Site Number : 2500004

Paris, 75019, France

Location

Investigational Site Number :2500003

Villejuif, 94800, France

Location

Investigational Site Number :5280002

Amsterdam, 1081 HV, Netherlands

Location

Investigational Site Number :5280003

Groningen, 9713 GZ, Netherlands

Location

Investigational Site Number : 5280005

Nijmegen, 6525 GA, Netherlands

Location

Investigational Site Number :5280001

Rotterdam, 3015 CE, Netherlands

Location

Investigational Site Number :5280004

Utrecht, 3584 CS, Netherlands

Location

Related Links

• TCD17197 Plain Language Results Summary

MeSH Terms

Conditions

Precursor Cell Lymphoblastic Leukemia-Lymphoma; Myelodysplastic Syndromes

Condition Hierarchy (Ancestors)

Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Bone Marrow Diseases

Limitations and Caveats

The study was terminated after completion of dose escalation phase of adult and pediatric arms and dose expansion/optimization phase of adult arm (Cohort A1), for non-safety related reasons. Dose expansion/optimization part of adult (Cohorts A2, B and C) and pediatric arms (Cohort D) were not initiated.

Results Point of Contact

• Title: Trial Transparency Team
• Organization: Sanofi aventis recherche & développement

Contact-US@sanofi.com

800-633-1610

Study Officials

• Clinical Sciences & Operations

  Sanofi

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

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: October 19, 2021
• First Posted: October 20, 2021
• Study Start: December 8, 2021
• Primary Completion: June 13, 2025
• Study Completion: June 13, 2025
• Last Updated: July 6, 2026
• Results First Posted: July 6, 2026

Record last verified: 2026-06

Data Sharing

• IPD Sharing: Will share

Locations

AU (2); CN (2); US (10); FR (4); NL (5)