Overview

This is a single group, Phase 1, single-arm, dose escalation study to determine the candidate dose(s), and evaluate safety, tolerability, and preliminary anti-tumor activity of SAR445419 administered after fludarabine and cytarabine conditioning for the treatment of relapsed or refractory acute myeloid leukemia (R/R AML). Adult participants with R/R AML will be eligible for treatment.

The study is intended to assess the candidate dose(s) by the occurrence of dose-limiting toxicity (DLT) from start of chemotherapy until 28 days after the first administration of SAR445419.

The duration of the study for a participant will include:

• Screening period up to 21 days prior to initiating chemotherapy,
• Treatment period of 5 days chemotherapy followed by SAR445419 administered for 2 weeks and end of treatment visit 56 days after first SAR445419 administration,
• Survival follow-up period up to 1 year after the last participant has started treatment with SAR445419.

Eligibility

Inclusion Criteria:

Participant must be 18 years of age inclusive

        Participants with confirmed diagnosis of relapsed or primary refractory acute myeloid
        leukemia (AML), according to World Health Organization (WHO) classification, including:
          -  Participants with relapsed AML after allogeneic stem cells transplantation, including
             those who have received donor lymphocyte infusions,
          -  Isolated central nervous system (CNS) or extramedullary disease,
          -  At least 1 prior line of therapy which includes chemotherapy, hypomethylating agents,
             venetoclax or targeted therapy.
        Participants with a weight ≥42 kg.
        Exclusion Criteria:
          -  Second primary malignancy that requires active therapy. Adjuvant hormonal therapy is
             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 symptomatic severe acute respiratory syndrome
             coronavirus 2 (SARS-CoV-2) infection.
          -  Pregnant or breast-feeding women, female participants of childbearing potential, and
             male participants with female partners of childbearing potential who are not willing
             to avoid pregnancy by using a highly effective method of contraception (2 barrier
             method or 1 barrier method with a spermicide, intrauterine device, or hormonal
             contraception with inhibition of ovulation, for 2 weeks prior to the first dose of
             SAR445419, during treatment, and 6 months after the last dose of fludarabine). A woman
             is considered of childbearing potential, i.e., fertile, following menarche and until
             becoming postmenopausal unless permanently sterile.
          -  History of solid organ transplant, including corneal transplant.
          -  Receiving at the time of first SAR445419 administration corticosteroid as a
             concomitant medication with corticosteroid dose >10 mg/day of oral prednisone or the
             equivalent, except steroid inhaler, nasal spray, or ophthalmic solution
          -  Known contraindication to any of the non-investigational medicinal products (NIMPs)
             (fludarabine, cytarabine, acetaminophen and diphenhydramine).
          -  Concurrent treatment with other investigational drugs
        The above information is not intended to contain all considerations relevant to a potential
        participation in a clinical trial.