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

NCT04150029 | Terminated Phase 2 Results FDA Drug

• 2 other identifiers: CMBG453C122012019-000439-14
• Study Type: interventional
• Target: 90
• Locations: 10 countries
• Sites: 28

Brief Summary

This trial seeked to extend the preliminary findings of efficacy by evaluating MBG453 in combination with hypomethylating agents (HMA) and also Bcl-2 inhibitor venetoclax.

Conditions

Acute Myeloid Leukemia

Keywords

MBG453; Venetoclax; Azacitidine; Phase 2; AML; Acute myeloid Leukemia; Sabatolimab

Outcome Measures

Primary Outcomes (2)

• Incidence of Dose Limiting Toxicities (DLT)(Safety run-in Patients Only)

  A dose-limiting toxicity (DLT) is defined as an adverse event or abnormal laboratory value considered by the Investigator to be at least possibily related to MBG453 as a single contributor or in combination with other component(s) of study treatment that occurs during the DLT observation period and meets any of the criteria as per protolcol.

  From Cycle 1 Day 8 to end of Cycle 2; Cycle =28 Days

• Percentage of Participants Achieving Complete Remission (CR) (CR Rate)

  CR rate is defined as the percentage of participants achieving a complete remission (CR) as per investigator assessment (based on IWG Cheson et al 2003, ELN 2017 Dohner et al 2017).

  approx. 31 months

Secondary Outcomes (14)

• Measurable Residual Disease (MRD) - Negativity Rate: Full Study Population

  approx. 31 months

• Measurable Residual Disease (MRD) - Negativity Rate in Participants With Best Overall Response (BOR) of CR/CRi and Evaluable MRD

  approx. 31 months

• Duration of Complete Remission (CR)

  approx. 31 months

• Percentage of Participants Achieving a Complete Remission (CR) or Complete Remission With Incomplete Hematologic Blood Count Recovery (CRi) (CR/CRi Rate)

  approx. 31 months

• The Duration of Complete Remission (CR)/Complete Remission With Incomplete Blood Count Recovery (CRi)

  approx. 31 months

Study Arms (1)

MBG453+Venetoclax +Azacitidine

EXPERIMENTAL

Participants received MBG453 in combination with Venetoclax and Azacitidine

Drug: MBG453; Drug: Venetoclax; Drug: Azacitidine

Interventions

MBG453 DRUG

Solution for intravenous infusion

Also known as: Sabatolimab

MBG453+Venetoclax +Azacitidine

Venetoclax DRUG

Tablet for oral administration

MBG453+Venetoclax +Azacitidine

Azacitidine DRUG

Solution for subcutaneous injection or intravenous infusion

MBG453+Venetoclax +Azacitidine

Eligibility Criteria

• Age: 18 Years - 100 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (28)

25Uni of Alabama at Birmingham

Birmingham, Alabama, 35294, United States

Location

Yale University School Of Medicine

New Haven, Connecticut, 06520, United States

Location

Uni Of Iowa Hospitals And Clinics

Iowa City, Iowa, 52242, United States

Location

Dana Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

Mayo Clinic Rochester

Rochester, Minnesota, 55905, United States

Location

Memorial Sloan Kettering

New York, New York, 10017, United States

Location

Weill Cornell Medicine NY-Presb

New York, New York, 10021, United States

Location

Levine Cancer Insitute Carolinas Healthcare System

Charlotte, North Carolina, 28204, United States

Location

Duke Univ Medical Center

Durham, North Carolina, 27710, United States

Location

Chattanooga Onc And Hem Assoc PC

Chattanooga, Tennessee, 37404, United States

Location

MD Anderson Cancer Center University of Texas

Houston, Texas, 77030, United States

Location

Huntsman Cancer Institute Univ of Utah

Salt Lake City, Utah, 84112 0550, United States

Location

Novartis Investigative Site

Clayton, Victoria, 3168, Australia

Location

Novartis Investigative Site

Vancouver, British Columbia, V5Z 1M9, Canada

Location

Novartis Investigative Site

Toronto, Ontario, M5G 2M9, Canada

Location

Novartis Investigative Site

Montreal, Quebec, H3T 1E2, Canada

Location

Novartis Investigative Site

Paris, 75475, France

Location

Novartis Investigative Site

Toulouse, 31059, France

Location

Novartis Investigative Site

Leipzig, Saxony, 04103, Germany

Location

Novartis Investigative Site

Berlin, 13353, Germany

Location

Novartis Investigative Site

Milan, MI, 20162, Italy

Location

Novartis Investigative Site

Roma, RM, 00133, Italy

Location

Novartis Investigative Site

Fukushima, Fukushima, 960 1295, Japan

Location

Novartis Investigative Site

Yamagata, Yamagata, 990 9585, Japan

Location

Novartis Investigative Site

Seoul, Seocho gu, 06591, South Korea

Location

Novartis Investigative Site

Barcelona, 08036, Spain

Location

Novartis Investigative Site

Madrid, 28009, Spain

Location

Novartis Investigative Site

Kaohsiung City, 83301, Taiwan

Location

Related Links

• A Plain Language Trial Summary is available on www.novctrd.com

MeSH Terms

Conditions

Leukemia, Myeloid, Acute

Interventions

sabatolimab; venetoclax; Azacitidine

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Aza Compounds; Organic Chemicals; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides

Results Point of Contact

• Title: Study Director
• Organization: Novartis Pharmaceuticals

novartis.email@novartis.com

862-778-3000

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: safety -run -in with escalating dose of MBG453 followed by expansion

Study Record Dates

• First Submitted: October 22, 2019
• First Posted: November 4, 2019
• Study Start: September 1, 2020
• Primary Completion: October 25, 2024
• Study Completion: October 25, 2024
• Last Updated: January 13, 2026
• Results First Posted: November 17, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will share

Locations

TW (1); IT (2); ES (2); US (12); CA (3); FR (2); AU (1); DE (2); JP (2); KR (1)