SC-2038: An open-label, first-in-human, dose-escalation/expansion study of SAR443579 administered as single agent by intravenous infusion in adult and pediatric 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)
SC-2038_SAR443579
What is the goal of the study?
There is growing evidence to suggest that acute myeloid leukemia (AML) derives from leukemia stem cells (LSCs) that give rise to leukemic blasts in vitro and in vivo models. It is hypothesized that the persistence of LSCs causes relapse after an initial remission. Thus, the eradication of LSCs may be a requirement for cure and is an important therapeutic goal. One potential therapeutic target in AML is the surface receptor CD123, the interleukin (IL)-3 receptor alpha chain (ILand blasts in most pediatric, young adolescent, and adult participants with AML, regardless of the prognostic risk group based on cytogenetic and molecular analyses. CD123 is also expressed in a variety of other hematologic disorders or malignancies including high-risk myelodysplastic syndrome (HR-MDS), blastic plasmacytoid dendritic cell neoplasm (BPDCN), and B-lineage acute lymphocytic or lymphoblastic leukemia (B-ALL). Based on the safety and tolerability data generated from the adult participants, SAR443579 will be further investigated in pediatric participants with high unmet need, similar disease biology, and comparable benefit risk profile. The proposed study is a first-in-human, dose finding study to determine the safety, pharmacokinetic (PK), pharmacodynamic (PDy) and preliminary efficacy of SAR443579 administered IV to pediatric arm (1 to 17 years old participants) and adolescent/adult arm (≥12 years old) There is growing evidence to suggest that acute myeloid leukemia (AML) derives from leukemia stem cells (LSCs) that give rise to leukemic blasts in vitro and in vivo models. It is hypothesized that the persistence of LSCs causes relapse after an initial remission. Thus, the eradication of LSCs may be a requirement for cure and is an important therapeutic goal. One potential therapeutic target in AML is the surface receptor CD123, the interleukin (IL)-3 receptor alpha chain (ILand blasts in most pediatric, young adolescent, and adult participants with AML, regardless of the prognostic risk group based on cytogenetic and molecular analyses. CD123 is also expressed in a variety of other hematologic disorders or malignancies including high-risk myelodysplastic syndrome (HR-MDS), blastic plasmacytoid dendritic cell neoplasm (BPDCN), and B-lineage acute lymphocytic or lymphoblastic leukemia (B-ALL). Based on the safety and tolerability data generated from the adult participants, SAR443579 will be further investigated in pediatric participants with high unmet need, similar disease biology, and comparable benefit risk profile. SAR443579 is a bispecific IgG-like monoclonal antibody with a competent Fc domain. SAR443579 functions as an NK cell engager (NKCE) by binding NKp46 and CD16 on the surface of the NK cell and CD123 on the malignant cell. Co-engagement of NK cell and malignant cell by SAR443579 induces NK cell activation and results in killing of CD123-expressing malignant cells via both immune synapse formation and antibody-dependent cellular cytotoxicity (ADCC). This results in potent cytotoxicity activity against the human AML cell lines expressing various densities of CD123. The co-engagement of NK and CD123-positive cells by SAR443579 against human MOLM-13 AML cells leads to NK activation, degranulation and expression of effector molecules. This leads to significant increase in survival of mice engrafted with MOLM-13. SAR443579 also induces dose-dependent blast cell killing when primary blasts from participants with AML are co-cultured with healthy donor NK cells. The proposed study is a first-in-human, dose finding study to determine the safety, pharmacokinetic (PK), pharmacodynamic (PDy) and preliminary efficacy of SAR443579 administered IV to pediatric arm (1 to 17 years old participants) and adolescent/adult arm.
Who can participate in the study?
Please contact the study team listed below to learn more.