An Open-label, First-in-human, Dose-escalation/Expansion Study of SAR443579 Administered as Single Agent by Intravenous Infusion in Participants With Relapsed or Refractory Acute Myeloid Leukemia (R/R AML), B-cell Acute Lymphoblastic Leukemia (B-ALL) or High Risk-myelodysplasia (HR-MDS) SAR443579

What's the purpose of this trial?

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.

This trial is currently open and accepting patients.

What will happen during the trial?

You may be able to join this trial if you:

The following criteria is a partial list of reasons why patients may be eligible to participate in this clinical trial. Further evaluation with a medical professional is required.

Inclusion Criteria:

- Participant must be ≥12 years old at the time the trial participant or legal guardian signs the informed consent form.

For participants of the Escalation Part only:

- Confirmed diagnosis of primary or secondary AML \[any subtype except acute promyelocytic leukemia (APL)\] according to World Health Organization (WHO) classification. Patients with AML must meet one of the following criteria, a), b) or c) 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.

Examples include but are not limited to:

* One cycle of high dose cytarabine (HiDAC) containing regimen
* One cycle of liposomal cytarabine and daunorubicin
* Two cycles of standard dose cytarabine containing regimen 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:

1. 4 cycles of hypomethylating agents (HMA) or
2. 2 cycles HMA + venetoclax b) Early relapse (ER) AML, defined as AML in relapse with CR duration \< 6 months from most recent treatment c) Leukemia in first or higher relapse

* Confirmed diagnosis of cluster of differentiation 123 (CD123) + HR-MDS, with a Revised International Prognostic Scoring System (IPSS-R) risk category of intermediate or higher and are limited to those with no available (or are ineligible) therapy with known clinical benefit.
* Not eligible for induction therapy and having completed ≥2 cycles of any of the following: hypomethylating agent (eg, 5 azacitidine or decitabine) and/or venetoclax, chemotherapy, or targeted agents.
* Not eligible for autologous stem cell transplant (ASCT) and having completed ≥1 course of induction therapy.

* Confirmed diagnosis of CD123 + B-ALL without extramedullary lesions that have no available (or are ineligible) therapy with known clinical benefit.

For Participants in the Expansion Part Only:

* For participants in Cohort A: Participants meeting inclusion criteria for AML patients that have been primary refractory (PIF) to prior induction treatment or who have had ER occurring 6 months or less after an initial remission on prior induction treatment.
* For participants in Cohort B: Participants meeting inclusion criteria for AML patients that have had late relapse (LR), occurring more than 6 months after an initial remission on prior induction treatment.
* Body weight \>40 kg. -- Body weight \>40 kg. - - -

Exclusion Criteria:

* Eastern Cooperative Oncology Group (ECOG) performance status \>2 (≥18 years-old). Karnovsky Scale (16-17 years-old) \<50% or Lansky Scale (\<16 years-old) \<50%.
* Ongoing or recent (within 5 years) evidence of significant autoimmune disease that requires or required treatment with systemic immunosuppressive treatments, which may suggest a risk for immune-related adverse events. The following are not exclusionary: vitiligo, childhood asthma that has resolved, residual hypothyroidism that required only hormone replacement or psoriasis that does not require systemic treatment.
* History of an invasive malignancy that requires active therapy (adjuvant hormonal therapy is allowed) other than the one treated in this study, with the exception of resected/ablated basal or squamous-cell carcinoma of the skin or carcinoma in situ of the cervix, or other local tumors considered cured by local treatment.
* Evidence of active central nervous system leukemia at the time of enrollment as evidenced by cytology or pathology.
* 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.
* 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 \>10 mg/day of oral prednisone or the equivalent,
* AML 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.
* Radiotherapy, even if palliative in intent, may not be given during the study.
* Prophylactic use of hematopoietic growth factors (eg, granulocyte-colony stimulating factor (G-CSF), granulocyte-macrophage colony-stimulating factor (GM-CSF), erythropoietin) during the DLT observation period in the Dose Escalation Part only. - Individuals accommodated in an institution because of regulatory or legal order; prisoners or participants who are legally institutionalized.
* Pregnant and breast-feeding women.
* History of solid organ transplant, including corneal transplant.
* Average QTc (using the Fridericia correction calculation) \>470 millisecond (msec) at screening.

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

Additional Trial Information

Phase 1/2

Enrollment: 82 patients (estimated)

View More

Published Results

A first-in-human study of CD123 NK cell engager SAR443579 in relapsed or refractory acute myeloid leukemia, B-cell acute lymphoblastic leukemia, or high-risk myelodysplasia

January 27, 2023

With a cutoff date of January 27, 2023, total 23 patients with R/R AML across 6 DLs (3 patients DL1 and 4 each in DL2 - DL6) were included in the safety population. The median age was 70 years (range: 21 - 80) with 9 patients (39.1%) reporting prior hematopoietic stem cell transplantation (HSCT) and 16 (69.6%) had prior exposure to venetoclax. Patients received a median of 2 cycles (range: 1 – 7) for median duration of 7 weeks (range: 1 - 25) and escalating doses of SAR’579 between 10 - 3000 µg/kg/dose in cycle 1 and 100 - 3000 µg/kg QW for the rest of induction cycles. No dose limiting toxicities (DLTs) were observed among the 21 DLT-evaluable patients, until highest dose of 3000 µg/kg QW. The most common treatment emergent adverse events (TEAEs) included infusion-related reactions (n = 10 [43.5%]) and nausea (n = 7 [30.4%]). TEAEs were reported in 22 patients (95.7%) with grade 3/4 adverse events (AEs) in 18 (78.3%) and treatment-related AEs in 16 patients (69.6%), respectively. There were 2 cases of cytokine release syndrome (n = 1 grade 1 and n = 1 grade 2) and no case of immune effector cell-associated neurotoxicity syndrome. No patient reported TEAE leading to permanent discontinuation of SAR’579. The CRc rate was 13.0% (3/23 patients evaluable for response). In DLs with a highest dose of 1000 µg/kg QW, 3/8 (37.5%) patients achieved a CR (2 CR/1 CRi). The median time to first CR/CRi was 16.1 weeks 95% confidence interval (8.1 – Not Estimable [NE]), and the median duration of CR/CRi is NE due to limited follow-up time. Conclusions: SAR’579 was well tolerated up to doses of 3000 µg/kg QW with observed clinical benefit in patients with R/R AML. The trial continues to accrue patients.

Trial Locations

All Trial Locations

View all clinical trial locations sorted by state.


City of Hope Comprehensive Cancer Center Beckman Research Institute

Duarte, CA

Open and Accepting


Winship Cancer Institute of Emory University (Main Campus)

Atlanta, GA

Open and Accepting


Beth Israel Deaconess Medical Center

Boston, MA

Open and Accepting

New York

Montefiore Medical Center

Bronx, NY

Open and Accepting

Weill Cornell

New York, NY

Open and Accepting


Oregon Health and Science University OHSU Knight Cancer Institute

Portland, OR

Open and Accepting


MD Anderson Cancer Center The University of Texas

Houston, TX

Open and Accepting
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