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Myelodysplastic SyndromesPhase 1NCT04810611

Phase Ib Study of Select Drug Combinations in Patients With Lower Risk MDS

A Phase 1 study testing MBG453, NIS793 and canakinumab in people with Myelodysplastic Syndromes, run by Novartis Pharmaceuticals at 13 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 this study was to characterize the safety, tolerability and confirm the dose for select single agents and combinations in patients with lower risk (very low, low, and intermediate risk) MDS. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Myelodysplastic Syndromes
What is being tested?
MBG453, NIS793 and canakinumab
Could I receive a placebo?
No, everyone receives an active treatment
How many people
33 participants
Where
13 sitesin 7 countries
Study dates
18 Jun 2021to 19 Apr 2024
Phase
Phase 1
Are there results?
None posted in the registry

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.
  • Patients must be ≥ 18 years of age at the time of signing the informed consent form (ICF).
  • Patients must have a diagnosis prior to participation in the study of IPSS-R very low, low, or intermediate risk MDS with ≤10% bone marrow blasts and one or more of the following:
  • Symptomatic anemia with hemoglobin <10 g/dL that has relapsed after or is refractory to ESAs (or the patient is intolerant to ESAs)
  • Symptomatic anemia with hemoglobin <10 g/dL) that is ESA-naive with EPO level ≥ 500 /uL
  • Thrombocytopenia with platelets <30,000/uL or with clinically significant bleeding or bruising and platelets <50,000/uL
Show all 10Show fewer
  • Neutropenia with an absolute neutrophil count (ANC) <500/ µL or with recurrent and/or severe infections and an ANC that is <1000/ µL and amenable to response assessments by International Working Group (IWG) response criteria in myelodysplasia (Cheson et al 2006)
  • Patients who are refractory to, intolerant of, or ineligible/unable to receive SOC therapeutic options including lenalidomide
  • Eastern Cooperative Oncology Group (ECOG) performance status (PS) ≤2
  • Patient must be a candidate for serial bone marrow aspirate and/or biopsy according to the institutions' guidelines and be willing to undergo a bone marrow aspirate and/or biopsy at screening, during and at the end of therapy on this study -

Who cannot join

  • Systemic antineoplastic therapy (including cytotoxic chemotherapy, alpha-interferon, kinase inhibitors or other targeted small molecules, and toxin-immunoconjugates) or any experimental therapy within 14 days or 5 half-lives, whichever is longer, before the first dose of study treatment.
  • History of hypersensitivity to any of the study treatments or its excipients or to drugs of similar chemical classes.
  • Patients with chronic myelomonocytic leukemia (CMML) or myelodysplastic/myeloproliferative neoplasms (MDS/MPN)
  • Use of hematopoietic colony-stimulating growth factors (e.g. G-CSF, GM-CSF, M-CSF), thrombopoietin mimetics or ESAs anytime ≤ 2 weeks (or 5 half-lives, whichever is longer) prior to start of study treatment.
  • Systemic chronic corticosteroid therapy (>10 mg/day prednisone or equivalent) or any immunosuppressive therapy within 7 days of first dose of study treatment. Topical, inhaled, nasal and ophthalmic steroids are allowed.
  • For arms containing canakinumab: Patients with ANC < 500 /µL

Trial locations and contacts

13 sites in 7 countries.

13 sites in 7 countries

United States5 sites

  • Massachusetts General Hospital .

    Boston, Massachusetts, 02114

  • The Ohio State University Wexner Medical Center .

    Columbus, Ohio, 43210

  • City Of Hope National Med Center Oncology

    Duarte, California, 91010

  • MD Anderson Cancer Center/University of Texas MD Anderson

    Houston, Texas, 77030

  • H Lee Moffitt Cancer Center and Research Institute

    Tampa, Florida, 33612

Other trials in United States

Singapore2 sites

  • Novartis Investigative Site

    Singapore, 119228

  • Novartis Investigative Site

    Singapore, 169608

Other trials in Singapore

Spain2 sites

  • Novartis Investigative Site

    Barcelona, Catalonia, 08035

  • Novartis Investigative Site

    Salamanca, Castille and León, 37007

Other trials in Spain

Australia1 site

  • Novartis Investigative Site

    Prahran, Victoria, 3181

Other trials in Australia

Israel1 site

  • Novartis Investigative Site

    Tel Aviv, 6423906

Other trials in Israel

Italy1 site

  • Novartis Investigative Site

    Milan, MI, 20162

Other trials in Italy

South Korea1 site

  • Novartis Investigative Site

    Seoul, 03080

Other trials in South Korea

About this study

Official title: A Phase Ib, Multicenter, Open-label Platform Study of Select Drug Combinations in Adult Patients With Lower Risk (Very Low, Low, or Intermediate Risk) Myelodysplastic Syndrome

The purpose of this study was to characterize the safety, tolerability and confirm the dose for select single agents and combinations in patients with lower risk (very low, low, and intermediate risk) MDS.

Read the detailed description

This was a phase Ib, multi center, open-label, platform study with multiple treatment arms.

The design of this study was adaptive to allow discontinuation of poorly tolerated or ineffective treatments and to facilitate the introduction of new candidate single agents or combinations. Study design included a dose escalation/confirmation part and a dose expansion.

The planned initial single agent and combination treatment arms were the following:

  • Arm 1: MBG453 single agent
  • Arm 2: NIS793 single agent
  • Arm 3: canakinumab single agent
  • Arm 4: MBG453 + NIS793 combination
  • Arm 5: MBG453 + canakinumab combination Patients were treated in the dose confirmation/escalation part of the study in Arms 1, 2, 3 and 5. No patients were treated in Arm 4. The study did not progress into the expansion phase.
Being tested
MBG453, NIS793, canakinumab
Keywords
Myelodysplastic, 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.

  • MBG453Drug

    Also called sabatolimab

    Anti-TIM3 monoclonal antibody

  • NIS793Drug

    Anti-TGF-β monoclonal antibody

  • canakinumabDrug

    Also called ACZ885

    Anti-IL-1β monoclonal antibody

Study groups in NCT04810611
Study groupRoleWhat they receive
Arm 1: MBG453 single agentExperimentalTreatment with MBG453 single agent Q4W to confirm safety and tolerability of RD.
Receives: Drug: MBG453
Arm 2: NIS793 single agentExperimentalTreatment with NIS793 single agent Q3W to establish RD in this indication and confirm safety and tolerability.
Receives: Drug: NIS793
Arm 3: canakinumab single agentExperimentalTreatment with single agent canakinumab Q4W to confirm safety and tolerability of RD.
Receives: Drug: canakinumab
Arm 4: MBG453 + NIS793 combinationExperimentalTreatment with combination of MBG453 and NIS793 Q3W to confirm safety and tolerability of combination RD.
Receives: Drug: MBG453; Drug: NIS793
Arm 5: MBG453 + canakinumab combinationExperimentalTreatment with MBG453 + canakinumab combination Q4W to confirm safety and tolerability of combination RD.
Receives: Drug: MBG453; Drug: canakinumab

What is being measured

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

  1. Dose interruption reduction

    Dose tolerability

    Measured: 30 Months

  2. Incidence of DLTs

    Incidence of dose limiting toxicities (DLTs) during the first 2 cycle of treatment during the dose escalation/confirmation part

    Measured: 30 Months

  3. Dose intensity

    Dose tolerability

    Measured: 30 Months

  4. AE and SAE incidence

    Incidence and severity of adverse events (AEs) and serious adverse events (SAEs) as per CTCAE v5.0, by treatment

    Measured: 30 months

Secondary outcomes (16)

  1. Reduction in red blood cell (RBC) / platelet transfusions from baseline in transfusion dependent patients

    The number of red cell or platelet transfusions a patient receives over the course of study treatment will be compared to the patient's baseline transfusion requirements based on the number of transfusions received during the 16-weeks period prior to the start of study treatment.

    Measured: Baseline, 30 Months

  2. Duration of transfusion independence lasting for >=8 weeks, >=12 weeks, >=16 weeks, >=24 weeks in transfusion dependent patients

    Red cell or platelet transfusion independence is defined as no red cell or platelet transfusions with a duration lasting for 8, 12, 16, or 24 weeks.

    Measured: 30 Months

  3. Change from baseline in hemoglobin (Hb) in transfusion dependent and transfusion independent patients

    Hemoglobin levels over the course of the study will be compared to the patient's baseline level to monitor for improvements in anemia.

    Measured: Baseline, 30 Months

  4. Change from baseline in platelet count in transfusion dependent and transfusion independent patients

    Platelet count over the course of the study will be compared to the patient's baseline count to monitor for improvements in thrombocytopenia.

    Measured: Baseline, 30 Months

  5. Change from baseline in Absolute Neutrophil Count/White Blood Cells (ANC/WBC) in transfusion dependent and transfusion independent patients

    Platelet count over the course of the study will be compared to the patient's baseline count to monitor for improvements in thrombocytopenia.

    Measured: Baseline, 30 Months

  6. Best Overall Response (BOR) in transfusion dependent and transfusion independent patients

    BOR is the best disease response recorded from the start of the treatment until disease progression/relapse. The subject's BOR will be calculated based on investigator's response evaluations per International Working Group (IWG) criteria.

    Measured: 30 Months

  7. Time to onset of transfusion independence in transfusion dependent patients

    Time to onset of either red cell transfusion independence or platelet transfusion independence.

    Measured: 30 Months

  8. Time to onset of BOR in transfusion dependent and transfusion independent patients

    Time to onset of BOR is defined as the time between date of start of study treatment to the date of first onset of Partial Response (PR) or better response.

    Measured: 30 Months

  9. Duration of Response (DOR) in transfusion dependent and transfusion independent patients

    DOR is defined as the duration from the first documented onset of complete response (CR), complete remission with partial hematologic recovery (CRh), bone marrow CR (mCR) or PR to the date of disease progression (PD) or relapse or death due to myelodysplastic syndrome (MDS).

    Measured: 30 Months

  10. Overall Response Rate (ORR) in transfusion dependent and transfusion independent patients

    ORR is the proportion of subjects with a best overall response of either CR or CRh, or mCR or PR.

    Measured: 30 Months

  11. Progression free survival (PFS) in transfusion dependent and transfusion independent patients

    PFS is defined as the time from the start of treatment until death due to any reason, disease progression, or relapse, whichever comes first.

    Measured: 30 Months

  12. Time to progression (TTP) in transfusion dependent and transfusion independent patients

    TTP is the time from the start of treatment to the date of PD, relapse or death due to underlying cancer.

    Measured: 30 Months

  13. Characterize pharmacokinetics for single agents and combinations: Cmax

    Serum concentrations and derived PK parameters

    Measured: 30 Months

  14. Characterize pharmacokinetics for single agents and combinations: Tmax

    Serum concentrations and derived PK parameters

    Measured: 30 Months

  15. Characterize pharmacokinetics for single agents and combinations: Ctrough

    Serum concentrations and derived PK parameters

    Measured: 30 Months

  16. Characterize the prevalence of immunogenicity

    Anti-drug antibody prevalence at baseline and on treatment.

    Measured: 30 Months

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 start18 Jun 2021
  3. Primary completion19 Apr 2024
  4. Study completion19 Apr 2024

Why it stopped: Business reasons

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 1
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
33 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04810611
Sponsor's protocol ID
CMBG453E12101
Other IDs
2019-004623-21, 2019
Status last verified
Oct 2025
First submitted
9 Mar 2021
Last updated
10 Oct 2025
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing MBG453, NIS793 and canakinumab in people with Myelodysplastic Syndromes, run by Novartis Pharmaceuticals at 13 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 10 inclusion and 6 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 10 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 13 sites in United States, Singapore, Spain, Australia, Israel 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

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

Are results available for this study?

The study was stopped early (reason given: Business reasons). Results are not available in the source record.

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?

Dose interruption reduction (time frame: 30 Months). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04810611.

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 10 Oct 2025.

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