STIMULUS MDS-US : Sabatolimab Added to HMA in Higher Risk MDS

NCT04878432 | Terminated Phase 2 Results FDA Drug

• 1 other identifier: CMBG453B1US01
• Study Type: interventional
• Target: 39
• Locations: 1 country
• Sites: 15

Brief Summary

The main objective of this study was to assess the safety profile of MBG453 (sabatolimab) in combination with FDA approved hypomethylating agents (HMAs) of investigator's choice (IV Decitabine or Azacitidine /SC Azacitidine /Oral Decitabine (cedazuridine combination (INQOVI))).

Conditions

Myelodysplastic Syndrome (MDS)

Keywords

sabatolimab; phase II; MBG453; TIM-3; decitabine; azacitidine; oral decitabine; INQOVI; myelodysplastic syndrome (MDS); adult; MDS

Outcome Measures

Primary Outcomes (1)

• Number of Participants With Treatment Emergent Adverse Events and Serious Adverse Events

  An adverse event (AE) is any untoward medical occurrence (e.g. any unfavorable and unintended sign \[including abnormal laboratory findings\], symptom or disease) in a participant or clinical investigation participant after providing written informed consent for participation in the study. Therefore, an AE may or may not be temporally or causally associated with the use of a medicinal (investigational) product.

  Adverse events are reported from the first dose of study medication up to approximately 24 months plus 30 - 150 day safety follow up dependent on HMA, for a maximum timeframe of approximately 29 months.

Secondary Outcomes (16)

• Number of Participants With Complete Remission According to International Working Group (IWG) for MDS (2006) With MBG453 (Sabatolimab) in Combination With HMAs (IV/SC/Oral) by 12 Months.

  up to Month 12

• Number of Participants With Progression Free Survival - Death and Disease Progression

  up to Month 24

• Progression Free Survival - 50th Percentile

  up to Month 24

• Progression Free Survival - Percent Probability - Kaplan-Meier Probability Estimates

  Months 6 and 12

• Overall Survival - Number of Participants Who Died

  up to Month 24

Study Arms (1)

MBG453 (sabatolimab) + HMA

EXPERIMENTAL

MBG453 (sabatolimab) + HMA of investigator's choice (IV Decitabine or Azacitidine /SC Azacitidine /Oral Decitabine (cedazuridine combination (INQOVI)))

Drug: MBG453; Drug: Azacitidine; Drug: Decitabine; Drug: INQOVI (oral decitabine)

Interventions

MBG453 DRUG

Solution for intravenous infusion

Also known as: sabatolimab

MBG453 (sabatolimab) + HMA

Azacitidine DRUG

Solution for subcutaneous injection or intravenous administration

MBG453 (sabatolimab) + HMA

Decitabine DRUG

Solution for intravenous administration

MBG453 (sabatolimab) + HMA

INQOVI (oral decitabine) DRUG

Tablet for oral administration

MBG453 (sabatolimab) + HMA

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Signed informed consent was obtained prior to participation in the study.
• Age ≥ 18 years at the date of signing the informed consent form (ICF).
• Morphologically confirmed diagnosis of a myelodysplastic syndrome (MDS) primary or secondary based on 2016 WHO classification by Investigator assessment with one of the following prognostic risk categories, based on the International Prognostic Scoring System (IPSS-R).. Note: MDS diagnosis history were recorded in the CRF:
• Very high (\> 6 points)
• High (\> 4.5 to ≤ 6 points)
• Intermediate (\> 3 to ≤ 4.5 points)
• Not suitable at the time of Screening for immediate myeloablative/chemotherapy or HSCT based on Investigator assessment of age, comorbidities, local guidelines, institutional practice (any or all of these).
• Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2.
• AST and ALT ≤ 3 × upper limit of normal (ULN).
• Total bilirubin ≤ 2 × ULN (except in the setting of isolated Gilbert syndrome).
• Estimated glomerular filtration rate ≥ 30 mL/min/1.73 m2 (estimation based on modification of diet in renal disease formula, by local laboratory).
• Patient was able to communicate with the Investigator and had the ability to comply with the requirements of the study procedures.

You may not qualify if:

• Prior exposure to TIM-3 directed therapy at any time. Prior therapy with immune checkpoint inhibitors (e.g., anti-CTLA4, anti-PD-1, anti-PD-L1, or anti-PD-L2), cancer vaccines were allowed only if the last dose of the drug was administered more than 4 months prior to enrollment.
• Previous treatment for intermediate, high or very high risk MDS (based on IPSS-R) with chemotherapy or other antineoplastic agents including lenalidomide and hypomethylating agent (HMAs) such as decitabine or INQOVI (oral decitabine) or azacitidine (patients who had up to 1 cycle of HMAs were included). However, previous treatment with hydroxyurea was permitted.
• Diagnosis of acute myeloid leukemia (AML) including acute promyelocytic leukemia and extra-medullary acute myeloid leukemia based on WHO 2016 classification.
• Diagnosis of Chronic myelomonocytic leukemia (CMML), or primary or secondary myelofibrosis based on 2016 WHO classification.
• History of organ transplant or allogenic HSCT.
• Patients with prior malignancy, except:
• Patients with history of lower risk Myelodysplastic syndrome (MDS) treated by supportive care (e.g., growth factors, transforming growth factor- beta agents) or untreated were eligible.
• Patients with history of lower risk MDS who were treated adequately with lenalidomide and then failed were eligible.
• Patients with history of adequately treated malignancy for which no anticancer systemic therapy (namely chemotherapy, radiotherapy or surgery) was ongoing or required during the course of the study. Patients who were receiving adjuvant therapy such as hormone therapy were eligible.
• Patients with MDS based on 2016 WHO classification with revised International Prognostic Scoring System (IPSS-R) ≤ 3.

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (15)

Mayo Clinic Arizona

Phoenix, Arizona, 85054, United States

Location

Arizona Oncology Associates

Tucson, Arizona, 85745, United States

Location

SCRI-Colorado Blood Cancer Institute

Denver, Colorado, 80218, United States

Location

Yale University School Of Medicine

New Haven, Connecticut, 06520, United States

Location

Advent Health Orlando

Orlando, Florida, 32803, United States

Location

Uni of Massachusetts Medical Center

Worcester, Massachusetts, 01655, United States

Location

University Of Michigan

Ann Arbor, Michigan, 48109, United States

Location

Karmanos Cancer Institute

Detroit, Michigan, 48201, United States

Location

Tisch Hospital NYU Langone

New York, New York, 10016, United States

Location

Mount Sinai Medical Center

New York, New York, 10029-6574, United States

Location

Duke Cancer Institute

Durham, North Carolina, 27710, United States

Location

University Hospitals Of Cleveland

Cleveland, Ohio, 44106, United States

Location

Cleveland Clinic

Cleveland, Ohio, 44195, United States

Location

Uni Of TX MD Anderson Cancer Cntr

Houston, Texas, 77030, United States

Location

Texas Oncology San Antonio USO

San Antonio, Texas, 78240, United States

Location

Related Links

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

MeSH Terms

Conditions

Myelodysplastic Syndromes

Interventions

sabatolimab; Azacitidine; Decitabine; decitabine and cedazuridine drug combination

Condition Hierarchy (Ancestors)

Bone Marrow Diseases; 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

+ 1 862 778 8300

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: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 5, 2021
• First Posted: May 7, 2021
• Study Start: March 17, 2022
• Primary Completion: October 26, 2023
• Study Completion: September 1, 2024
• Last Updated: October 16, 2025
• Results First Posted: July 31, 2025

Record last verified: 2025-10

Data Sharing

• IPD Sharing: Will share

Locations

US (15)