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

A Phase II Multi-center, Single Arm, Safety and Efficacy Study of MBG453 in Combination With Azacitidine and Venetoclax for the Treatment of Acute Myeloid Leukemia (AML) in Adult Patients Unfit for Chemotherapy

ClinicalTrials.gov Identifier: NCT04150029

Novartis Reference Number: CMBG453C12201

Last Update: Dec 10, 2020

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All compounds are either investigational or being studied for (a) new use(s). Efficacy and safety have not been established. There is no guarantee that they will become commercially available for the use(s) under investigation. 

Study Description

This trial will seek to extend the preliminary findings of efficacy of MBG453 in combination with hypomethylating agents (HMA) by evaluating MBG453 in combination with the HMA azacitidine and the Bcl-2 inhibitor venetoclax. The primary purpose of Part 1 (Safety Run-in) is to rule out excessive toxicity of MBG453, when administered in combination with azacitidine and venetoclax. The primary purpose of the combined Part 1 and Part 2 (Safety run-in and Expansion Part) is to evaluate efficacy of MBG453, when administered in combination with azacitidine and venetoclax in adult patients with newly diagnosed AML, who are not suitable for treatment with intensive chemotherapy.

Acute Myeloid Leukemia
Phase 2
Overall status 
Enrollment count 
86 participants
Start date 
Sep 01, 2020
Completion date 
Jan 20, 2026
18 Years and older (Adult, Older Adult)


Solution for intravenous infusion
Tablet for oral administration
Solution for subcutaneous injection or intravenous infusion

Eligibility Criteria

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 30 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
Subjects with therapy related AML.
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

Other protocol-defined Inclusion/Exclusion may apply.

Study Locations

United States
Yale University School of Medicine
New Haven, 06520
United States
Memorial Sloan Kettering Dept. of MSKCC
New York, 10017
New York
United States
Huntsman Cancer Institute Univ of Utah
Salt Lake City, 84112 0550
United States
Novartis Investigative Site
Vancouver, V5Z 1M9
British Columbia
Novartis Investigative Site
Montreal, H3T 1E2


Novartis Pharmaceuticals
Novartis Pharmaceuticals

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