Myelodysplastic Syndrome (MDS)Phase 2NCT04878432
STIMULUS MDS-US : Sabatolimab Added to HMA in Higher Risk MDS
A Phase 2 study testing MBG453, Azacitidine and Decitabine in people with Myelodysplastic Syndrome (MDS), run by Novartis Pharmaceuticals at 15 sites in United States.
Trial 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))). Read more about this study
- Who is it for?
- Ages 18 to 99 years
- Conditions the study is for
- Myelodysplastic Syndrome (MDS)
- What is being tested?
- MBG453, Azacitidine and Decitabine
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 39 participants
- Where
- 15 sitesUnited States
- Study dates
- 17 Mar 2022to 1 Sep 2024
- Phase
- Phase 2
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 99 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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)
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- 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.
Who cannot join
- 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:
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- 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.
Trial locations and contacts
15 sites in 1 country.
15 sites in 1 country
United States15 sites
University Of Michigan
Ann Arbor, Michigan, 48109
University Hospitals Of Cleveland
Cleveland, Ohio, 44106
Cleveland Clinic
Cleveland, Ohio, 44195
SCRI-Colorado Blood Cancer Institute
Denver, Colorado, 80218
Karmanos Cancer Institute
Detroit, Michigan, 48201
Duke Cancer Institute
Durham, North Carolina, 27710
Uni Of TX MD Anderson Cancer Cntr
Houston, Texas, 77030
Yale University School Of Medicine
New Haven, Connecticut, 06520
Tisch Hospital NYU Langone
New York, New York, 10016
Mount Sinai Medical Center
New York, New York, 10029-6574
Advent Health Orlando
Orlando, Florida, 32803
Mayo Clinic Arizona
Phoenix, Arizona, 85054
Texas Oncology San Antonio USO
San Antonio, Texas, 78240
Arizona Oncology Associates
Tucson, Arizona, 85745
Uni of Massachusetts Medical Center
Worcester, Massachusetts, 01655
About this study
Official title: 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))).
Read the 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:
- Screening period (signing of written informed consent through day of enrollment),
- Core phase for up to 12 months,
- Extension phase for efficacy and/or survival status (up to 12 months after the core phase),
- 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.
- Conditions
- Myelodysplastic Syndrome (MDS)
- Being tested
- MBG453, Azacitidine, Decitabine, INQOVI (oral decitabine)
- Keywords
- sabatolimab, phase II, MBG453, TIM-3, decitabine, azacitidine, oral decitabine, INQOVI, myelodysplastic syndrome (MDS), adult, MDS
- Medical subject headings
- Myelodysplastic Syndromes
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MBG453Drug
Also called sabatolimab
Solution for intravenous infusion
AzacitidineDrug
Solution for subcutaneous injection or intravenous administration
DecitabineDrug
Solution for intravenous administration
INQOVI (oral decitabine)Drug
Tablet for oral administration
| Study group | Role | What they receive |
|---|---|---|
| MBG453 (sabatolimab) + HMA | Experimental | MBG453 (sabatolimab) + HMA of investigator's choice (IV Decitabine or Azacitidine /SC Azacitidine /Oral Decitabine (cedazuridine combination (INQOVI))) Receives: Drug: MBG453; Drug: Azacitidine; Drug: Decitabine; Drug: INQOVI (oral decitabine) |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
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.
Measured: 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).
Measured: 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).
Measured: 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).
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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
Measured: 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.
Measured: up to Month 24
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 May 2021
- Study start17 Mar 2022
- Primary completion26 Oct 2023
- Study completion1 Sep 2024
Why it stopped: Lack of efficacy in the program as demonstrated in the earlier CMBG453B12301 (STIMULUS MDS-2) study.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Myelodysplastic Syndrome (MDS)Studies of the same condition, open and under way.
- More trials run by Novartis PharmaceuticalsThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 39 participants (actual)
Sponsor and investigators
- Lead sponsor
- Novartis Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Novartis Pharmaceuticals, Study director, Novartis Pharmaceuticals
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04878432
- Sponsor's protocol ID
- CMBG453B1US01
- Status last verified
- Oct 2025
- First submitted
- 5 May 2021
- Last updated
- 16 Oct 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: 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/.