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

NCT ID: NCT04810611

Last Updated: 2025-10-10

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE1
• Total Enrollment: 33 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-06-18
• Study Completion Date: 2024-04-19

Brief 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.

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.

Conditions

Myelodysplastic Syndromes

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Arm 1: MBG453 single agent

Treatment with MBG453 single agent Q4W to confirm safety and tolerability of RD.

Group Type: EXPERIMENTAL

MBG453

Intervention Type: DRUG

Anti-TIM3 monoclonal antibody

Arm 2: NIS793 single agent

Treatment with NIS793 single agent Q3W to establish RD in this indication and confirm safety and tolerability.

Group Type: EXPERIMENTAL

NIS793

Intervention Type: DRUG

Anti-TGF-β monoclonal antibody

Arm 3: canakinumab single agent

Treatment with single agent canakinumab Q4W to confirm safety and tolerability of RD.

Group Type: EXPERIMENTAL

canakinumab

Intervention Type: DRUG

Anti-IL-1β monoclonal antibody

Arm 4: MBG453 + NIS793 combination

Treatment with combination of MBG453 and NIS793 Q3W to confirm safety and tolerability of combination RD.

Group Type: EXPERIMENTAL

MBG453

Intervention Type: DRUG

Anti-TIM3 monoclonal antibody

NIS793

Intervention Type: DRUG

Anti-TGF-β monoclonal antibody

Arm 5: MBG453 + canakinumab combination

Treatment with MBG453 + canakinumab combination Q4W to confirm safety and tolerability of combination RD.

Group Type: EXPERIMENTAL

MBG453

Intervention Type: DRUG

Anti-TIM3 monoclonal antibody

canakinumab

Intervention Type: DRUG

Anti-IL-1β monoclonal antibody

Interventions

MBG453

Anti-TIM3 monoclonal antibody

Intervention Type: DRUG

NIS793

Anti-TGF-β monoclonal antibody

Intervention Type: DRUG

canakinumab

Anti-IL-1β monoclonal antibody

Intervention Type: DRUG

Other Intervention Names

sabatolimab; ACZ885

Eligibility Criteria

Inclusion Criteria

1. Signed informed consent must be obtained prior to participation in the study.

2. Patients must be ≥ 18 years of age at the time of signing the informed consent form (ICF).

3. 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:

1. Symptomatic anemia with hemoglobin <10 g/dL that has relapsed after or is refractory to ESAs (or the patient is intolerant to ESAs)

2. Symptomatic anemia with hemoglobin <10 g/dL) that is ESA-naive with EPO level ≥ 500 /uL

3. Thrombocytopenia with platelets <30,000/uL or with clinically significant bleeding or bruising and platelets <50,000/uL

4. 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)

4. Patients who are refractory to, intolerant of, or ineligible/unable to receive SOC therapeutic options including lenalidomide

5. Eastern Cooperative Oncology Group (ECOG) performance status (PS) ≤2

6. 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 -

Exclusion Criteria

1. 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.

2. History of hypersensitivity to any of the study treatments or its excipients or to drugs of similar chemical classes.

3. Patients with chronic myelomonocytic leukemia (CMML) or myelodysplastic/myeloproliferative neoplasms (MDS/MPN)

4. 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.

5. 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.

6. For arms containing canakinumab: Patients with ANC < 500 /µL

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Novartis Pharmaceuticals

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

City Of Hope National Med Center Oncology

Duarte, California, United States

H Lee Moffitt Cancer Center and Research Institute

Tampa, Florida, United States

Massachusetts General Hospital .

Boston, Massachusetts, United States

The Ohio State University Wexner Medical Center .

Columbus, Ohio, United States

MD Anderson Cancer Center/University of Texas MD Anderson

Houston, Texas, United States

Novartis Investigative Site

Prahran, Victoria, Australia

Novartis Investigative Site

Tel Aviv, , Israel

Novartis Investigative Site

Milan, MI, Italy

Novartis Investigative Site

Singapore, , Singapore

Novartis Investigative Site

Singapore, , Singapore

Novartis Investigative Site

Seoul, , South Korea

Novartis Investigative Site

Salamanca, Castille and León, Spain

Novartis Investigative Site

Barcelona, Catalonia, Spain

Countries

United States; Australia; Israel; Italy; Singapore; South Korea; Spain

Related Links

https://www.novctrd.com/ctrdweb/trialresult/trialresults/pdf?trialResultId=18275

Study Results

https://www.novctrd.com/ctrdweb/patientsummary/patientsummaries?patientSummaryId=2574

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

Other Identifiers

2019-004623-21

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

CMBG453E12101

Identifier Type: -

Identifier Source: org_study_id