A Study to Investigate Natural Killer Cell Engager (SAR443579) With Different Agents in Participants With Hematological Malignancies

Prior treatment

• Known second malignancy either progressing or requiring active treatment within the last 3 years prior to first IMP administration
• Known acquired immunodeficiency syndrome (AIDS-related illnesses) or HIV disease requiring antiretroviral treatment, or having active hepatitis B or C infection, or SARS-CoV-2 infection. With exception for:
  • HBV as determined by positive test for hepatitis B surface antigen (HBsAg) and/or HBV DNA. Participant who tested positive for anti-hepatitis B core (HBc) antigen IgG (with or without testing positive for anti-HBs), but tested negative for HBsAg and HBV DNA, was eligible.
  • A participant who tested positive for anti-HCV antibodies and had undetectable HCV RNA without receiving antiviral treatment for HCV was eligible.
• Active, known, or suspected clinically significant autoimmune disease that had required systemic treatment in the past 2 years prior to first IMP administration, except controlled by replacement therapy (eg, thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc)
• Medical conditions requiring treatment with medications with narrow therapeutic index that were substrates of CYP enzymes and that could not be closely monitored to allow for dose adjustment.
• Ongoing adverse event of NCI CTCAE [Version 5.0] Grade 2 or greater severity cause by any prior anti-cancer therapy
  • Substudy 01:
• Participant had received treatment with at least one of the following:
  • A hypomethylating agent, venetoclax and/or chemo therapeutic agent for AML other than hydroxyurea used for disease control prior to the initiation of study therapy.
  • Experimental therapies for AML.
  • Concomitant medications of strong and moderate CYP3A inducers within 7 days prior to the initiation of study treatment.
  • The above information was not intended to contain all considerations relevant to a participant's potential participation in a clinical trial.

Other illness

• Any clinically significant, uncontrolled medical conditions (including any serious active systemic infection that was not controlled)
• Cardiovascular disease of New York Heart Association (NYHA) Class ≥2.
• Malabsorption syndrome or other condition that precludes enteral route of administration

Lab values

• A baseline QTc interval of (using the Fridericia correction calculation) >470 msec.

Other

• Predicted life expectancy ≤3 months.
• Patient with Acute Promyelocytic Leukemia (APL)
• Known active central nervous system involvement with AML at the time of enrollment as evidenced by cytology or pathology

• Participants with CD123-expressing hematological neoplasm per the 5th edition of the WHO Classification of Hematolymphoid Tumors.
  • Substudy 01:
• Participants must be ≥18 years of age
• Confirmed diagnosis of Acute Myeloid Leukemia
• Ineligible for intensive chemotherapy. Ineligible for intensive chemotherapy was defined by the following criteria:
• ≥ 75 years of age, OR
• 18 to 74 years of age and meeting one or more of the following:
• Eastern Cooperative Oncology Group (ECOG) performance status 2-3.
• Cardiac history of congestive heart failure (CHF) requiring treatment or left ventricular ejection fraction (LVEF) ≤50% or symptomatic coronary heart disease confirmed by coronarography or cardiac imaging.
• Diffusing capacity of the lungs for carbon monoxide (DLCO) ≤65% or forced expiratory volume (FEV1) ≤65%.
• Creatinine clearance ≥30 to <45 mL/min calculated by modification of diet in renal disease (MDRD) formula.
• Moderate hepatic impairment with total bilirubin >1.5 to ≤3.0x upper limit of normal (ULN).
  • Participant with an Eastern Cooperative Oncology Group (ECOG) performance status as follows:
• 0 to 2 for participants ≥75 years of age or b) 0 to 3 for participants 18 to 74 years of age.
• For participants ≥75 years of age, adequate renal function demonstrated by a creatinine clearance ≥30 mL/min, calculated by modification of diet in renal disease (MDRD)
• Participant with adequate liver function demonstrated by the following:
  • For participants 18 to 74 years of age, aspartate aminotransferase (AST) ≤3.0 × ULN, alanine aminotransferase (ALT) ≤3.0 × ULN and bilirubin ≤3.0 × ULN, unless considered due to leukemic organ involvement ˂5 × ULN.
  • For participants ≥75 years of age, aspartate aminotransferase (AST) ≤3.0 × ULN, alanine aminotransferase (ALT) ≤3.0 × ULN and bilirubin ≤1.5 × ULN, unless considered due to leukemic organ involvement ˂5 × ULN.