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)

Sanofi

Status and phase: Terminated; Phase 2; Phase 1

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

Treatments: Drug: SAR443579

Study type: Interventional

Funder types: Industry

Identifiers

NCT05086315

TCD17197

2021-004287-98 (EudraCT Number)

2023-508357-58 (Registry Identifier)

U1111-1266-7399 (Registry Identifier)

Details and patient eligibility

About

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.

Full description

Study duration per participant is 2.5 years.

Enrollment: 101 patients

Sex: All

Ages: 1+ year old

Volunteers: No Healthy Volunteers

Inclusion criteria

• 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:

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, 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:

     1. intermediate or high-risk category as per a Revised International Prognostic Scoring System (IPSS-R) AND
     2. confirmed CD123 + expression status determined by local institutional standards AND
     3. 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.

   • Pediatric arm and escalation part only: Confirmed diagnosis of BPDCN according to World Health Organization (WHO) 2022 classification, who have relapsed or refractory disease with no available (or are ineligible) therapy with known clinical benefit.

   • Japan participants (Cohort C): Participant must be at least 18 years old at the time the trial participant signs the informed consent form

Exclusion criteria

• 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%.
• 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 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.

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

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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101 participants in 1 patient group

SAR443579

Experimental group

Description:

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.

Treatment:

Drug: SAR443579