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

Single-arm, Open Label, Phase II Study of MBG453 (Sabatolimab) Added to FDA Approved Hypomethylating Agents of Investigator's Choice (IV/SC/Oral) for Patients With Intermediate, High or Very High Risk Myelodysplastic Syndrome (MDS) as Per IPSS-R Criteria (US Multi-center) (STIMULUS MDS-US)

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))).

Study Overview

• Status: Terminated
• Conditions: Myelodysplastic Syndrome (MDS)
• Intervention / Treatment: Drug: MBG453; Drug: INQOVI (oral decitabine); Drug: Azacitidine; Drug: Decitabine

Detailed Description

This was a single arm, nonrandomized, open label, Phase II multicenter study of i.v sabatolimab added to FDA approved HMA agents of Investigator's choice (i.v/s.c/oral) in adult patients with intermediate, high or very high risk MDS as per IPSS-R criteria.

There were 4 separate periods of this study:

1. Screening period (signing of written informed consent through day of enrollment),
2. Core phase for up to 12 months,
3. Extension phase for efficacy and/or survival status (up to 12 months after the core phase),
4. Post-treatment safety follow-up period monitoring for AEs for 30 days following the last dose of azacitidine or decitabine or INQOVI (oral decitabine), or 150 days following the last dose of sabatolimab, whichever was later.

During the conduct of the study there were 2 updates to the Novartis development strategy for sabatolimab. Based on the results from the Phase II STIMULUS MDS-1 study, recruitment was halted for CMBG453B1US01 (STIMULUS MDS-US) on 30-Sep-2022. Novartis confirmed the decision to halt recruitment was not based on any safety findings or safety concerns. Patients who were on study treatment or in follow-up were continued as per the protocol. Furthermore, on 11-Jan-2024, all sabatolimab investigators were notified by Novartis that, based on decision taken in Dec-2023, that the sabatolimab development program (which included study CMBG453B1US01) would be terminated. After the decision was made to discontinue the sabatolimab development program, participants already enrolled in the CMBG453B1US01 study were prepared for closure; these close out activities took approximately 9 months. The actual last patient last visit date was 1 Sep 2024.

• Study Type: Interventional
• Enrollment (Actual): 39
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Phoenix, Arizona, United States, 85054
      • Mayo Clinic Arizona
    • Tucson, Arizona, United States, 85745
      • Arizona Oncology Associates
  • Colorado
    • Denver, Colorado, United States, 80218
      • SCRI-Colorado Blood Cancer Institute
  • Connecticut
    • New Haven, Connecticut, United States, 06520
      • Yale University School of Medicine
  • Florida
    • Orlando, Florida, United States, 32803
      • Advent Health Orlando
  • Massachusetts
    • Worcester, Massachusetts, United States, 01655
      • Uni of Massachusetts Medical Center
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • University of Michigan
    • Detroit, Michigan, United States, 48201
      • Karmanos Cancer Institute
  • New York
    • New York, New York, United States, 10029-6574
      • Mount Sinai Medical Center
    • New York, New York, United States, 10016
      • Tisch Hospital NYU Langone
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Duke Cancer Institute
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic
    • Cleveland, Ohio, United States, 44106
      • University Hospitals of Cleveland
  • Texas
    • Houston, Texas, United States, 77030
      • Uni Of TX MD Anderson Cancer Cntr
    • San Antonio, Texas, United States, 78240
      • Texas Oncology San Antonio USO

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 99 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Key inclusion criteria:

1. Signed informed consent was obtained prior to participation in the study.
2. Age ≥ 18 years at the date of signing the informed consent form (ICF).

3. 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)
4. 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).
5. Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2.
6. AST and ALT ≤ 3 × upper limit of normal (ULN).
7. Total bilirubin ≤ 2 × ULN (except in the setting of isolated Gilbert syndrome).
8. Estimated glomerular filtration rate ≥ 30 mL/min/1.73 m2 (estimation based on modification of diet in renal disease formula, by local laboratory).
9. Patient was able to communicate with the Investigator and had the ability to comply with the requirements of the study procedures.

Key exclusion criteria

1. 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.
2. 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.
3. Diagnosis of acute myeloid leukemia (AML) including acute promyelocytic leukemia and extra-medullary acute myeloid leukemia based on WHO 2016 classification.
4. Diagnosis of Chronic myelomonocytic leukemia (CMML), or primary or secondary myelofibrosis based on 2016 WHO classification.
5. History of organ transplant or allogenic HSCT.

6. Patients with prior malignancy, except:

   1. 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.
   2. Patients with history of lower risk MDS who were treated adequately with lenalidomide and then failed were eligible.
   3. 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.
7. Patients with MDS based on 2016 WHO classification with revised International Prognostic Scoring System (IPSS-R) ≤ 3.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: MBG453 (sabatolimab) + HMA; MBG453 (sabatolimab) + HMA of investigator's choice (IV Decitabine or Azacitidine /SC Azacitidine /Oral Decitabine (cedazuridine combination (INQOVI)))	Drug: MBG453; Solution for intravenous infusion; Other Names: sabatolimab; Drug: INQOVI (oral decitabine); Tablet for oral administration; Drug: Azacitidine; Solution for subcutaneous injection or intravenous administration; Drug: Decitabine; Solution for intravenous administration

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Complete remission rate was assessed according to International Working Group (IWG) for MDS (2006) with MBG453 (sabatolimab) in combination with HMAs (IV/SC/Oral) in Participants with intermediate, high, or very high risk MDS by 12 months.	up to Month 12
Number of Participants With Progression Free Survival - Death and Disease Progression	Defined as time from enrollment to disease progression (including transformation to leukemia per WHO 2016 classification), relapse from CR according to IWG-MDS or death due to any cause, whichever occurs first, as per investigator assessment by 12 months post last patient first treatment (LPFT).	up to Month 24
Progression Free Survival - 50th Percentile	Defined as time from enrollment to disease progression (including transformation to leukemia per WHO 2016 classification), relapse from CR according to IWG-MDS or death due to any cause, whichever occurs first, as per investigator assessment by 12 months post last patient first treatment (LPFT).	up to Month 24
Progression Free Survival - Percent Probability - Kaplan-Meier Probability Estimates	Defined as time from enrollment to disease progression (including transformation to leukemia per WHO 2016 classification), relapse from CR according to IWG-MDS or death due to any cause, whichever occurs first, as per investigator assessment by 12 months post last patient first treatment (LPFT).	Months 6 and 12
Overall Survival - Number of Participants Who Died	Overall Survival (OS) is defined as the time from the first dose of study medication to death due to any cause.	up to Month 24
Overall Survival - 50th Percentile	Overall Survival (OS) is defined as the time from the first dose of study medication to death due to any cause.	up to Month 24
Overall Survival - Percent Probability - Kaplan-Meier Probability Estimates	Overall Survival (OS) is defined as the time from the first dose of study medication to death due to any cause.	up to Month 24
Leukemia-free Survival - Number of Participants Who Died and Number of Participants Who Progressed to Leukemia	Leukemia-free survival (LFS) is the time from the date of the first dose of medication to ≥ 20% blasts in bone marrow/peripheral blood (per WHO 2016 classification) or death due to any cause.	up to Month 24
Leukemia-free Survival - 50th Percentile	Leukemia-free survival (LFS) is the time from the date of the first dose of medication to ≥ 20% blasts in bone marrow/peripheral blood (per WHO 2016 classification) or death due to any cause.	up to Month 24
Leukemia-free Survival - Percent Probability - Kaplan-Meier Probability Estimates	Leukemia-free survival (LFS) is the time from the date of the first dose of medication to ≥ 20% blasts in bone marrow/peripheral blood (per WHO 2016 classification) or death due to any cause.	Months 6 and 12
Percentage of Participants With Complete Remission, Marrow Complete Remission and/or Partial Remission	Percentage of complete remission, marrow complete remission, and/or partial remission according to IWG-MDS remission criteria as per investigator assessment	up to Month 24
Time to Complete Remission	Time to Complete Remission is defined as the time from the date of the first dose of study medication to the first documented CR.	up to Month 24
Improvement in Packed RBCs Transfusion Independence - Mean Total Duration (Weeks) of Transfusion Independence Post-baseline	RBC/Platelets transfusion independence is defined as a participant having received <0 units RBC/Platelets transfusions during at least 8 consecutive weeks after enrollment.	up to Month 24
Number of Participants With Improvement in Packed RBCs Transfusion Independence - At Least One Period of Transfusion Independence Post Baseline	RBC/Platelets transfusion independence rate is defined as the percentage of participants having received <0 units RBC/Platelets transfusions during at least 8 consecutive weeks after enrollment.	up to Month 24
Improvement in Platelets Transfusion Independence - Mean Total Duration (Weeks) of Transfusion Independence Post-baseline	RBC/Platelets transfusion independence is defined as a participant having received <0 units RBC/Platelets transfusions during at least 8 consecutive weeks after enrollment	up to Month 24
Number of Participants With Improvement in Platelets Transfusion Independence - At Least One Period of Transfusion Independence Post Baseline	RBC/Platelets transfusion independence rate is defined as the proportion of participants having received <0 units RBC/Platelets transfusions during at least 8 consecutive weeks after enrollment.	up to Month 24

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals
• Investigators: Study Director: Novartis Pharmaceuticals, Novartis Pharmaceuticals

Publications and helpful links

Helpful Links

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

Study record dates

Study Major Dates

• Study Start (Actual): March 17, 2022
• Primary Completion (Actual): October 26, 2023
• Study Completion (Actual): September 1, 2024

Study Registration Dates

• First Submitted: May 5, 2021
• First Submitted That Met QC Criteria: May 5, 2021
• First Posted (Actual): May 7, 2021

Study Record Updates

• Last Update Posted (Estimated): October 16, 2025
• Last Update Submitted That Met QC Criteria: October 8, 2025
• Last Verified: October 1, 2025

More Information

Terms related to this study

• Keywords: adult; MDS; TIM-3; phase II; MBG453; decitabine; sabatolimab; azacitidine; oral decitabine; INQOVI; myelodysplastic syndrome (MDS)
• Additional Relevant MeSH Terms: Hematologic Diseases; Bone Marrow Diseases; Hemic and Lymphatic Diseases; Myelodysplastic Syndromes; Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleic Acids, Nucleotides, and Nucleosides; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Aza Compounds; Nucleosides; Ribonucleosides; Decitabine; Azacitidine; decitabine and cedazuridine drug combination; sabatolimab
• Other Study ID Numbers: CMBG453B1US01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD 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 review 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 availability is according to the criteria and process described on https://www.clinicalstudydatarequest.com/.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No