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

Eligibility Criteria

• * Participants must be ≥18 years of age
• * Confirmed diagnosis of Acute Myeloid Leukemia
• * Ineligible for intensive chemotherapy. Ineligible for intensive chemotherapy is defined by the following criteria:
• 1. Eastern Cooperative Oncology Group (ECOG) performance status 2-3.
• 2. 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.
• 3. Diffusing capacity of the lungs for carbon monoxide (DLCO) ≤65% or forced expiratory volume (FEV1) ≤65%.
• 4. Creatinine clearance ≥30 to \<45 mL/min calculated by modification of diet in renal disease (MDRD) formula.
• 5. Moderate hepatic impairment with total bilirubin \>1.5 to ≤3.0x upper limit of normal (ULN).
• * Subject with an Eastern Cooperative Oncology Group (ECOG) performance status as follows:
• * 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)
• * Subject with adequate liver function demonstrated by the following:
• 1. 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.
• 2. 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.
• * Any clinically significant, uncontrolled medical conditions (including any serious active systemic infection that is not controlled)
• * 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:
• 1. HBV as determined by positive test for hepatitis B surface antigen (HBsAg) and/or HBV DNA. Participant who tests positive for anti-hepatitis B core (HBc) antigen IgG (with or without testing positive for anti-HBs), but tests negative for HBsAg and HBV DNA, is eligible.
• 2. A participant who tests positive for anti-HCV antibodies and has undetectable HCV RNA without receiving antiviral treatment for HCV is eligible.
• * Active, known, or suspected clinically significant autoimmune disease that has 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)
• * Predicted life expectancy ≤3 months.
• * Medical conditions requiring treatment with medications with narrow therapeutic index that are substrates of CYP enzymes and that cannot 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
• * 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
• * Cardiovascular disease of New York Heart Association (NYHA) Class ≥2.
• * Malabsorption syndrome or other condition that precludes enteral route of administration
• * A baseline QTc interval of (using the Fridericia correction calculation) \>470 msec.
• * Subject has received treatment with at least one of the following:
• 1. 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.
• 2. Experimental therapies for AML.
• 3. Concomitant medications of strong and moderate CYP3A inducers within 7 days prior to the initiation of study treatment.