Relatlimab With Nivolumab and 5-Azacytidine for the Treatment of AML

Inclusion Criteria: Cohort 1 (R/R AML): \- Patients with AML who have failed first line induction chemotherapy (consisting of a minimum of two intensive chemotherapy cycles, e.g. 7+3 or HAM) or patients with AML who have relapsed after achieving complete remission (CR), CRi, or CRp, or patients who have failed up to one prior salvage therapy Cohort 2 (frontline older AML): \- Patients aged ≥65 years with previously untreated AML who are unfit for or decline standard induction therapy. General inclusion criteria: * Patients not eligible for intensive induction chemotherapy and/or allogeneic stem cell transplant. * Age ≥18 years * ECOG Performance Status ≤2 * Adequate organ function: Total bilirubin ≤2 x ULN (≤3 × ULN if due to leukemic involvement or Gilbert's syndrome) AST and ALT ≤2.5 × ULN (≤5.0 × ULN if due to leukemic involvement) Serum creatinine ≤2 × ULN or glomerular filtration rate (GFR) ≥50 mL/h * Adequate cardiac function: TTE with documented LVEF ≥50% * At least 2 weeks OR at least 5 half-lives interval from prior treatment to time of initiation of study medication * GvHD of grade ≤A on ≤10 mg prednisone without any additional immunosuppressive therapies (tacrolimus, ciclosporin, etc.) * Written informed consent * Negative pregnancy test and adequate methods of contraception for females of childbearing potential, adequate methods of contraception for males Exclusion Criteria: * Acute promyelocytic leukemia (APL) * Biphenotypic or bilineage leukemia * Known allergy or hypersensitivity to 5-azacytidine, nivolumab, relatlimab, or any of their components * History of life-threatening toxicity related to prior immune therapy * Previous treatment with immunotherapeutic drugs targeting PD-1/PD-L1 in combination with 5-azacytidine * Previous treatment with LAG-3 targeted agents * Known history of severe interstitial lung disease or severe pneumonitis * Known history (active, known, or suspected) of any of the following autoimmune diseases: inflammatory bowel disease rheumatoid arthritis systemic progressive sclerosis systemic lupus erythematosus autoimmune vasculitis * Active uncontrolled pneumonitis * Active uncontrolled infection * Symptomatic or poorly controlled CNS leukemia * Confirmed history of encephalitis, meningitis, or uncontrolled seizures in the year prior to informed consent * Uncontrolled or significant cardiovascular disease * Troponin T (TnT) or I (TnI) \> 2 × institutional ULN * Organ allografts * Allogeneic hematopoietic stem cell transplantation within the last 100 days before first study drug administration * Active GvHD \> grade A * Known human immunodeficiency virus seropositivity * Known positivity for hepatitis B by surface antigen expression or active hepatitis C infection * Other medical, psychological, or social condition that may interfere with study participation or compliance, or compromise patient safety * Patients unwilling or unable to comply with the protocol * Patients who are pregnant or breastfeeding * Prisoners and subjects who are compulsory detained