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Myelodysplastic Syndrome (MDS)Phase 2STIMULUS-MDS3NCT04812548

A Study of Sabatolimab in Combination With Azacitidine and Venetoclax in High or Very High Risk MDS Participants

A Phase 2 study testing sabatolimab, azacitidine and venetoclax in people with Myelodysplastic Syndrome (MDS), run by Novartis Pharmaceuticals at 10 sites in 7 countries.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial summary

The purpose of the study was to find out if the new drug sabatolimab when given in combination with azacitidine and venetoclax, was safe and had beneficial effects in participants with high or very high risk myelodysplastic syndrome (MDS) who were not suitable for treatment with intensive chemotherapy or a stem-cell… Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Myelodysplastic Syndrome (MDS)
What is being tested?
sabatolimab, azacitidine and venetoclax
Could I receive a placebo?
No, everyone receives an active treatment
How many people
20 participants
Where
10 sitesin 7 countries
Study dates
31 May 2021to 8 May 2023
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

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 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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)
  • Morphologically confirmed diagnosis of myelodysplastic syndrome (MDS) based on 2016 WHO classification (Arber et al, 2016) by local investigator assessment with one of the following Prognostic Risk Categories, based on the revised International Prognostic Scoring System (IPSS-R) (Greenberg et al 2012):
  • Very high (> 6 points)
  • High (> 4.5-6 points)
  • Not immediately eligible for hematopoietic stem-cell transplantation (HSCT) or intensive chemotherapy at the time of screening due to individual clinical factors such as age, comorbidities and performance status, donor availability (de Witte et al 2017)
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2

Who cannot join

  • Prior exposure to TIM-3 directed therapy or any BCL-2 inhibitor (including venetoclax) at any time
  • Prior therapy with immune check point inhibitors (e.g. anti-CTLA4, anti-PD-1, anti-PD-L1, or anti-PD-L2) or cancer vaccines is not allowed if the last dose of the drug was administered within 4 months prior to start of treatment
  • Previous first-line treatment for very high risk or high risk myelodysplastic syndromes (based on IPSS-R,Greenberg et al 2012 and Arber et al, 2016) with any antineoplastic agents, approved or investigational, including for example chemotherapy, lenalidomide and hypomethylating agents (HMAs) such as decitabine or azacitidine However, a one single cycle of HMAs treatment only started prior to enrollment is allowed.
  • Live vaccine administered within 30 days prior to start of treatment
  • Current use or use within 14 days prior to start of treatment 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
  • History of severe hypersensitivity reactions to any ingredient of study drug(s) (azacitidine, venetoclax or sabatolimab) or monoclonal antibodies (mAbs) and/or their excipients
  • Participants with Myelodysplastic syndrome (MDS) based on 2016 WHO classification (Arber et al, 2016) with revised International Prognostic Scoring System (IPSS-R) ≤ 4.5

Trial locations and contacts

10 sites in 7 countries.

10 sites in 7 countries

France2 sites
  • Novartis Investigative Site

    Marseille, 13273

  • Novartis Investigative Site

    Nice, 06202

Other trials in France

Germany2 sites
  • Novartis Investigative Site

    Düsseldorf, 40479

  • Novartis Investigative Site

    Stuttgart, 70376

Other trials in Germany

Greece2 sites
  • Novartis Investigative Site

    Alexandroupoli, Evros, 681 00

  • Novartis Investigative Site

    Pátrai, 265 00

Other trials in Greece

Belgium1 site
  • Novartis Investigative Site

    Brasschaat, 2930

Other trials in Belgium

Hungary1 site
  • Novartis Investigative Site

    Nyíregyháza, 4400

Other trials in Hungary

Italy1 site
  • Novartis Investigative Site

    Genova, GE, 16132

Other trials in Italy

Spain1 site
  • Novartis Investigative Site

    Barcelona, Catalonia, 08036

Other trials in Spain

About this study

Official title: A Single-arm, Open-label, Phase II Study of Sabatolimab in Combination With Azacitidine and Venetoclax in Adult Participants With High or Very High Risk Myelodysplastic Syndromes (MDS) as Per IPSS-R Criteria

The purpose of the study was to find out if the new drug sabatolimab when given in combination with azacitidine and venetoclax, was safe and had beneficial effects in participants with high or very high risk myelodysplastic syndrome (MDS) who were not suitable for treatment with intensive chemotherapy or a stem-cell transplant (HSCT).

Read the detailed description

Approximately 76 people with high or very high risk myelodysplastic syndrome (MDS) and age ≥ 18 years were to be asked to join this study but due to the decision by Novartis to halt recruitment the study did not enroll the approximately 76 participants.

The primary purpose of Part 1 (Safety run-in) was to rule out excessive toxicity of sabatolimab, when administered in combination with azacitidine and venetoclax. The primary purpose of the combined cohort 2 of the Safety run-in (Part 1) and Expansion (Part 2) was to have evaluated efficacy of sabatolimab, when administered in combination with azacitidine and venetoclax in adult participants with high or very high risk MDS. But due to the decision by Novartis to halt recruitment at the end of the Safety run-in, the study enrolled participants in Part 1 only.

This study was to have consisted of two parts:

Safety Run-in Part:

The first approximately 18 participants to have joined the study would have been part of the safety run-in. The first approximately 6 participants would have been enrolled to the lower dose given every four weeks sabatolimab safety run-in cohort.

After these participants would have completed 2 cycles of treatment a decision would have been made to confirm whether the chosen combination of sabatolimab with azacitidine and venetoclax was considered safe to continue with approximately 12 participants, to have been enrolled to the higher dose given every four weeks safety run-in cohort. After these participants would have completed 2 cycles of treatment a decision would have been made to confirm whether the chosen combination of sabatolimab with azacitidine and venetoclax was considered safe to continue with expansion part of the study.

Expansion Part (which did not occur):

After the safety run-in part would have confirmed that the study treatment (higher dose of sabatolimab given every four weeks with azacitidine and venetoclax) was safe, about 58 more participants would have been enrolled in the expansion part to better investigate the efficacy of the study treatment.

Being tested
sabatolimab, azacitidine, venetoclax
Keywords
MGM453, Phase II, sabatolimab, TIM-3, venetoclax, azacitidine, Myelodysplastic syndrome, 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.

  • sabatolimabDrug

    Also called MBG453

    Sabatolimab was administered at a low dose (Safety run-in (Part 1) cohort 1) or a high dose (Safety run-in (Part 1) cohort 2) via i.v. infusion over 30 minutes on Day 8 of every treatment cycle. Cycle = 28 days

  • azacitidineDrug

    A standard dose of azacitidine was given subcutaneously or intravenously every day for seven consecutive days on days 1-7 of a confirmed treatment cycle. In keeping with standard clinical practice, the alternative schedules for five consecutive days on days 1-5, followed by a two day break, then two consecutive days on days 8-9 was permitted (alternative schedule).

  • venetoclaxDrug

    Venetoclax film-coated tablets was administered at a dose of 400 mg orally or corresponding reduced dose for concomitant use with P-gp inhibitors or moderate or strong CYP3A4 inhibitors, once a day, from C1D1 to C1D14 during the treatment cycle. No ramp-up for venetoclax was necessary.

Study groups in NCT04812548
Study groupRoleWhat they receive
sabatolimab + azacitidine + venetoclaxExperimentalPart 1: Safety run-in consisted of 2 subsequent cohorts of a lower dose (cohort 1) and a higher dose (cohort 2) of sabatolimab in combination with fixed dose of venetoclax and azacitidine. Part 2 (did not start as recruitment was stopped in Part 1) Expansion was to enroll additional participants to further investigate the regimen including sabatolimab at the higher dose, azacitidine and venetoclax. Participants data from Part 1 and Part 2 treated with the higher dose was to have been combined to determine the complete remission rate.
Receives: Drug: sabatolimab; Drug: azacitidine; Drug: venetoclax

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Rate of Dose Limiting Toxicities (DLTs) - All Grades (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 possibly related to sabatolimab as a single contributor or in combination with other component(s) of study treatment that occurs during the DLT observation period and meets severity criteria as per protocol.

    Measured: From Cycle 1 Day 8 to end of Cycle 2 (Cycle = 28 Days)

  2. Percentage of Participants (Receiving 800mg Sabatolimab) Achieving Complete Remission (CR) Per Investigator Assessment

    This endpoint assessed Complete Remission (CR) Rate of participants from Cohort 2 of Part 1 and Part 2 according to Investigator assessment per modified IWG-MDS - Cheson 2006 criteria. CR is defined as follows: bone marrow blasts <=5%, hemoglobin level ≥ 10 g/dL, platelets count ≥ 100*10^9/L, neutrophils count ≥ 1.0*10^9/L, absence of blasts in peripheral blood.

    Measured: up to approx. 23 months

Secondary outcomes (16)
  1. Percentage of Subjects Achieving a Complete Remission (CR) + Morphologic Complete Remission (mCR): Safety run-in (Part 1)

    Assessed the durability of complete remission (CR) or morphologic complete remission (mCR) rate. mCR is defined as <=5% blasts and blast count decrease by >=50% compared to baseline as per modified IWG-MDS Cheson 2006 criteria.

    Measured: up to approx. 23 months

  2. Overall Response Rate (ORR) of Participants Who Achieved Hematologic Improvement (HI) or Better as Best Response

    The percentage of participants achieving [CR + mCR + partial remission (PR) + hematologic improvement (HI)], per modified IWG-MDS Cheson 2006 criteria. Partial response (PR): all complete response (CR) criteria except >=50% decrease from baseline in blasts in bone marrow AND blast count in bone marrow >5%. HI (erythroid response or platelet response or neutrophil response) must last at least 8 weeks.

    Measured: up to approx. 23 months

  3. Percentage of Participants Who Are RBC/Platelets Transfusion Independent

    Improvement in red blood cells (RBC)/platelets transfusion post-baseline as per International Working Group - Myelodysplastic syndromes (IWG-MDS) by dose level for the safety run-in part (Cohort 1 (400 mg Q4W) and Cohort 2 (800 mg Q4W)) and for participants treated with sabatolimab 800 mg (Q4W) (Cohort 2 of safety run-in and expansion parts). RBC/Platelets transfusion independence is defined as participants having received no RBC/Platelets transfusions during at least 8 consecutive weeks after start of treatment.

    Measured: up to approx. 23 months

  4. Duration of Transfusion Independence

    Sum of each period of the transfusion independence for participants with at least one period of transfusion independence post-baseline by dose level for the safety run-in part (Cohort 1 (400 mg Q4W) and Cohort 2 (800 mg Q4W)) and for participants treated with sabatolimab 800 mg (Q4W) (Cohort 2 of safety run-in and expansion parts) for both red blood cells and platelets. RBC/Platelets transfusion independence is defined as participants having received no RBC/platelets transfusions during at least 8 consecutive weeks after start of treatment.

    Measured: up to approx. 23 months

  5. Peak Serum Concentration (Cmax) of Sabatolimab

    Maximal concentration of sabatolimab for participants treated with sabatolimab by dose level for the safety run-in part (Cohort 1 (400 mg Q4W) and Cohort 2 (800 mg Q4W)).

    Measured: Continuously collected for patients during treatment with sabatolimab up to 150 days after last treatment, approx. 23 months

  6. Trough Serum Concentration (Cmin) Sabatolimab

    Concentration of sabatolimab prior to next dosing or after end of treatment by dose level for the safety run-in part (Cohort 1 (400 mg Q4W) and Cohort 2 (800 mg Q4W)).

    Measured: Continuously collected for patients during treatment with sabatolimab up to 150 days after last treatment, approx. 23 months

  7. Anti-drug Antibody (ADA) Prevalence at Baseline and ADA Incidence On-treatment by Dose Level

    Immunogenicity of sabatolimab prior to sabatolimab exposure and during treatment

    Measured: Continuously collected for patients during treatment with sabatolimab up to 150 days after last treatment, approx. 23 months

  8. Duration of Complete Remission (CR)

    Duration of complete remission (CR) is defined as time from first occurrence of CR to relapse from CR, progression or death due to any cause whichever occurs first for the safety run-in part (Cohort 2 (800 mg Q4W)). CR is defined as follows: bone marrow blasts <=5%, hemoglobin level ≥ 10 g/dL, platelets count ≥ 100*10^9/L, neutrophils count ≥ 1.0*10^9/L, absence of blasts in peripheral blood.

    Relapse from complete remission (CR)is when at least 1 of the following criteria is met:

    1. Return to baseline bone marrow blast percentage.
    2. Decrease of ≥ 50% from maximum remission/response levels in neutrophils AND neutrophils <1.0*10^9/L.
    3. Decrease of ≥ 50% from maximum remission/response levels in platelets AND platelets <100*10^9/L.
    4. Decrease from maximum remission/response levels in Hgb concentration by ≥ 1.5g/dL AND Hgb < 10g/dL.
    5. Becoming transfusion dependent

    Measured: up to approx. 23 months

  9. Time to Complete Remission(CR)/Marrow Complete Remission (mCR)

    Time to CR/mCR is defined as time from start of treatment to first occurrence of CR or mCR as per investigator assessment for the safety run-in part (Cohort 2 (800 mg Q4W)).

    Measured: up to approx. 23 months

  10. Duration of Complete Response (CR)/Marrow Complete Response (mCR)

    Duration of CR/mCR is defined as time from first occurrence of CR/mCR to relapse from CR, progression or death due to any cause whichever occurs first for the safety run-in part (Cohort 2 (800 mg Q4W)).

    Measured: up to approx. 23 months

  11. Duration of Response for Participants Who Achieved Hematologic Improvement (HI) or Better

    The duration of response was derived for participants treated with sabatolimab at the higher dose who achieved HI or better as per investigator assessment and is defined from the first occurrence of complete response (CR), marrow complete response (mCR), partial response (PR) or hematologic improvement (HI) until relapse, progression or death due to any reason for the safety run-in part (Cohort 2 (800 mg Q4W)).

    Measured: up to approx. 23 months

  12. Progression-Free Survival (PFS)

    Time from start of treatment to disease progression (including transformation to acute leukemia per WHO 2016 classification), relapse from CR or death due to any cause, whichever occurs first for the safety run-in part (Cohort 2 (800 mg Q4W)).

    Measured: up to approx. 23 months

  13. Leukemia-Free Survival (LFS)

    Time from start of treatment to transformation to acute leukemias per investigator assessment [as defined as ≥ 20% blasts in bone marrow/ peripheral blood (per WHO 2016 classification) or diagnosis of extramedullary acute leukemia or death due to any cause, whichever occurs first for the safety run-in part (Cohort 2 (800 mg Q4W)).

    Measured: up to approx. 23 months

  14. Event-Free Survival (EFS)

    Time from start of treatment to lack of reaching CR within the first 6 cycles, relapse from CR or death due to any cause, whichever occurs first for the safety run-in part (Cohort 2 (800 mg Q4W)).

    Measured: up to approx. 23 months

  15. Overall Survival (OS)

    Time from start of treatment to death due to any cause for the safety run-in part (Cohort 2 (800 mg Q4W)).

    Measured: Date of start of treatment to date of death due to any reason, for up to approx. 23 months

  16. Changes in Fatigue (Part 2 - Expansion)

    Changes in fatigue as measured by the Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue for participants treated with sabatolimab at the higher dose of the expansion part only. Measurements would have been taken via scores from 0 (not at all) to 4 (very much). The higher the score, the better the Quality of Life.

    Measured: throughout study until progressive disease, death or study discontinuation, approx. 3 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted23 Mar 2021
  2. Study start31 May 2021
  3. Primary completion8 May 2023
  4. Study completion8 May 2023

Why it stopped: Study was stopped following a strategic decision from the Sponsor. It was not based on any safety findings or safety concerns with sabatolimab.

Resources

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
Sequential
Masking
None (open label)
Enrolment
20 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04812548
Sponsor's protocol ID
CMBG453B12203
Other IDs
2020-003669-21
Acronym
STIMULUS-MDS3
Status last verified
Sep 2025
First submitted
23 Feb 2021
Last updated
9 Oct 2025
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 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 www.clinicalstudydatarequest.com.

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing sabatolimab, azacitidine and venetoclax in people with Myelodysplastic Syndrome (MDS), run by Novartis Pharmaceuticals at 10 sites in 7 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 7 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 9 Oct 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 10 sites in France, Germany, Greece, Belgium, Hungary and 2 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 11 Jun 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Rate of Dose Limiting Toxicities (DLTs) - All Grades (Safety run-in Patients Only) (time frame: From Cycle 1 Day 8 to end of Cycle 2 (Cycle = 28 Days)). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Oct 2025.

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