A Study of MBG453 in Combination With Azacitidine and Venetoclax in AML Patients Unfit for Chemotherapy

Inclusion Criteria

• Signed informed consent must be obtained prior to participation in the study.
• Age ≥ 18 years at the date of signing the informed consent form (ICF)
• Newly diagnosed with AML based on 2016 WHO classification (Arber et al 2016) and not suitable for intensive chemotherapy defined as: age ≥75, ECOG performance Status 2 or 3, or any of the following comomorbitities: severe cardiac comorbities (including congestive heart failure, LVEF ≤ 50%, chronic stable Angina) , pulmonary comorbidity (DLCO ≤ 65% or FEVI ≤ 65%). moderate hepatic impairment (with total Bilirubin >1.5 to 3x ULN) , renal impairment (eGFR≥ 30 ml/min/1.73m^2 to <45 ml/min/1.73m^2), or other comorbidity incompatible with intensive chemotherapy per Investigator assessement and approved by the Novartis Medical monitor)
• Not planned for hematopoietic stem-cell transplantation (HSCT)
• Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 , 2 or 3

Exclusion Criteria

• Prior exposure to TIM-3 directed therapy
• History of severe hypersensitivity reactions to any ingredient of study drug(s) (azacitidine, venetoclax or MGB453) or monoclonal antibodies (mAbs) and/or their excipients
• Current use or use within 14 days prior to randomization of systemic, steroid therapy (> 10 mg/day prednisone or equivalent) or any immunosuppressive therapy. Topical, inhaled, nasal, ophthalmic steroids are allowed. Replacement therapy, steroids given in the context of a transfusion are allowed and not considered a form of systemic treatment.
• Previous treatment at any time, with any of the following antineoplastic agents, approved or investigational; checkpoint inhibitors, venetoclax and hypomethylating agents (HMAs) such as decitabine or azacitidine.
• Active autoimmune disease requiring systemic therapy (e.g.corticosteroids).
• Live vaccine administered within 30 Days prior to randomization