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A Study of MBG453 in Combination With Azacitidine and Venetoclax in AML Patients Unfit for Chemotherapy (STIMULUS-AML1)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT04150029
Recruitment Status : Recruiting
First Posted : November 4, 2019
Last Update Posted : December 7, 2021
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Acute Myeloid Leukemia Drug: MBG453 Drug: Venetoclax Drug: Azacitidine Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 86 participants
Allocation: N/A
Intervention Model: Sequential Assignment
Intervention Model Description: safety -run -in with escalating dose of MBG453 followed by expansion
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 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
Actual Study Start Date : September 1, 2020
Estimated Primary Completion Date : December 20, 2022
Estimated Study Completion Date : February 17, 2026

Arm Intervention/treatment
Experimental: MBG453+Venetoclax +Azacitidine
Patients will receive MBG453 in combination with Venetoclax and Azacitidine
Drug: MBG453
Solution for intravenous infusion
Other Name: Sabatolimab

Drug: Venetoclax
Tablet for oral administration

Drug: Azacitidine
Solution for subcutaneous injection or intravenous infusion

Primary Outcome Measures :
  1. Incidence of dose limiting toxicities (Safety run-in patients only) [ Time Frame: From Cycle 1 Day 8 to end of Cycle 2; Cycle =28 Days ]
    Assessment of tolerability of MBG in combination with venetoclax and azacitidine

  2. Percentage of subjects achieving complete remission (CR) [ Time Frame: at least 6 cycles from last patient first treatment up to 100 weeks (each cycle =28 Days) ]
    Assessing Complete Remission (CR) Rate (Safety run in (expansion dose Level only) + Expansion)

Secondary Outcome Measures :
  1. Percentage of subjects achieving a complete remission (CR) or complete remission with incomplete hematologic blood count recovery (CRi) [ Time Frame: every 12 weeks (starting at week 5) for up to 48 months from last patient first treatment ]
    Assessing the durability of complete remission (CR) or complete remission with incomplete hematologic blood count recovery (CRi) rate by determining the relapse free survival (RFS) in participants who achieve complete response (CR)

  2. Time from date of first documented CR or CRi to the date of first documented relapse or death due to any cause [ Time Frame: every 12 weeks (starting at week 5) for up to 48 months from last patient first treatment ]
    Time to relapse from CR/CRi or death (relapse free survival), whichever occurs first

  3. Time from the date of the first documented CR to the date of first documented relapse or death due to any cause [ Time Frame: every 12 weeks (starting at week 5) for up to 48 months from last patient first treatment ]
    Assessing the durability of complete remission (CR) by determining the Relapse Free Survival (RFS) in subjects who achieved CR, whichever occurs first

  4. Time from start of treatment until death, relapse from CR, or treatment failure, whichever occurs first [ Time Frame: every 12 weeks (starting at week 5) for up to 48 months from last patient first treatment ]
    Assessing event free survival (EFS).

  5. Time from start of treatment to death due to any cause (overall survival) [ Time Frame: date of start of treatment to date of death due to any reason (for up to 48 months from last patient first treatment) ]
    Time to death due to any cause to assess overall survival

  6. Peak Serum Concentration (Cmax) MBG453 [ Time Frame: Cycle 1 Day 8 (end of infusion) and Cycle 3 Day 8 (end of infusion), cycle = 28 days ]
    Maximal concentration of MBG453

  7. Trough Serum Concentration (Cmin) MBG453 [ Time Frame: Day 8 of Cycle 1,2,3,6,9,12,18, 24 and through treatment completion, an average of 24 months ]
    Concentration of MBG453 prior to next dosing or after end of treatment

  8. Trough Plasma Concentration (Cmin) Venetoclax [ Time Frame: Day 8 of Cycle 1, 3 and 8 ; Cycle =28 days ]
    Trough concentration of venetoclax on treatment

  9. Anti-drug Antibody (ADA) prevalence at baseline [ Time Frame: prior to first dose of MGB453 on Cycle 1 Day 8 (cycle =28 Days) ]
    Immunogenicity to MBG453 prior to MBG453 exposure

  10. ADA prevalence on-treatment [ Time Frame: Throughout study until 150 day safety follow-up ]
    Immunogenicity to MBG453 on Treatment and after treatment

  11. Percentage of MRD-negative subjects in the full study population and in subjects achieving CR or CRi [ Time Frame: every 12 weeks (starting at week 5) for up to 48 months from last patient first treatment ]
    Rate of MRD-negative subjects

  12. Rate of subjects who achieve transfusion independence from baseline and while on treatment. [ Time Frame: from start of treatment up to 48 months from last patient first treatment ]
    Percentage of subjects who are not dependent on blood transfusions for more than 8 weeks will be determined and related to the total number of patients participating to report percentage

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  1. Signed informed consent must be obtained prior to participation in the study.
  2. Age ≥ 18 years at the date of signing the informed consent form (ICF)
  3. 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)
  4. .Not planned for hematopoietic stem-cell transplantation (HSCT)
  5. .Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 , 2 or 3

Exclusion Criteria:

  1. Prior exposure to TIM-3 directed therapy
  2. History of severe hypersensitivity reactions to any ingredient of study drug(s) (azacitidine, venetoclax or MGB453) or monoclonal antibodies (mAbs) and/or their excipients
  3. 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.
  4. 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.
  5. Active autoimmune disease requiring systemic therapy (e.g.corticosteroids).
  6. Live vaccine administered within 30 Days prior to randomization

Other protocol-defined Inclusion/Exclusion may apply.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT04150029

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Contact: Novartis Pharmaceuticals 1-888-669-6682
Contact: Novartis Pharmaceuticals +41613241111

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United States, California
UCSF Medical Center Recruiting
San Francisco, California, United States, 94143
Contact: Erika Cavallone    415-353-1351   
Principal Investigator: Neil Dunavin         
United States, Connecticut
Yale University School of Medicine Recruiting
New Haven, Connecticut, United States, 06520
Contact: Victoria Lobo   
Principal Investigator: Amer Zeidan         
United States, Massachusetts
Dana Farber Cancer Institute Dana Farber Cancer Int Recruiting
Boston, Massachusetts, United States, 02215
Contact    617-632-3352      
Principal Investigator: Marlise Luskin         
United States, New York
Memorial Sloan Kettering Dept. of MSKCC Recruiting
New York, New York, United States, 10017
Contact: Cary Saito    646-227-2157   
Principal Investigator: Eytan Stein         
United States, Texas
MD Anderson Cancer Center/University of Texas MD Anderson Recruiting
Houston, Texas, United States, 77030
Contact: Hannah Acres    713-792-7305   
Principal Investigator: Guillermo Garcia-Manero         
United States, Utah
Huntsman Cancer Institute Univ of Utah Recruiting
Salt Lake City, Utah, United States, 84112 0550
Contact: David Samuel    801-585-0236   
Principal Investigator: Tibor Kovacsovics         
Australia, Victoria
Novartis Investigative Site Recruiting
Clayton, Victoria, Australia, 3168
Canada, British Columbia
Novartis Investigative Site Recruiting
Vancouver, British Columbia, Canada, V5Z 1M9
Canada, Ontario
Novartis Investigative Site Recruiting
Toronto, Ontario, Canada, M5G 1Z6
Canada, Quebec
Novartis Investigative Site Recruiting
Montreal, Quebec, Canada, H3T 1E2
Novartis Investigative Site Recruiting
Berlin, Germany, 13353
Novartis Investigative Site Recruiting
Leipzig, Germany, 04103
Novartis Investigative Site Recruiting
Milano, MI, Italy, 20162
Novartis Investigative Site Recruiting
Roma, RM, Italy, 00133
Novartis Investigative Site Recruiting
Fukushima city, Fukushima, Japan, 960 1295
Novartis Investigative Site Recruiting
Yamagata, Japan, 990 9585
Korea, Republic of
Novartis Investigative Site Recruiting
Seoul, Seocho Gu, Korea, Republic of, 06591
Novartis Investigative Site Recruiting
Barcelona, Catalunya, Spain, 08036
Novartis Investigative Site Recruiting
Madrid, Spain, 28009
Novartis Investigative Site Recruiting
Taoyuan, Taiwan, 33305
Sponsors and Collaborators
Novartis Pharmaceuticals
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Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
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Responsible Party: Novartis Pharmaceuticals Identifier: NCT04150029    
Other Study ID Numbers: CMBG453C12201
2019-000439-14 ( EudraCT Number )
First Posted: November 4, 2019    Key Record Dates
Last Update Posted: December 7, 2021
Last Verified: December 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description:

Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent expert panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.

This trial data is currently available according to the process described on


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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Novartis ( Novartis Pharmaceuticals ):
Phase 2
Acute myeloid Leukemia
Additional relevant MeSH terms:
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Leukemia, Myeloid
Leukemia, Myeloid, Acute
Neoplasms by Histologic Type
Antimetabolites, Antineoplastic
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Enzyme Inhibitors