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

NCT04810611 | Terminated Phase 1 FDA Drug

• 2 other identifiers: CMBG453E121012019-004623-21
• Study Type: interventional
• Target: 33
• Locations: 7 countries
• Sites: 13

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.

Conditions

Myelodysplastic Syndromes

Keywords

Myelodysplastic; myelodysplastic syndrome; MDS

Outcome Measures

Primary Outcomes (4)

• Dose interruption reduction

  Dose tolerability

  30 Months

• Incidence of DLTs

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

  30 Months

• Dose intensity

  Dose tolerability

  30 Months

• AE and SAE incidence

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

  30 months

Secondary Outcomes (16)

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

  Baseline, 30 Months

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

  30 Months

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

  Baseline, 30 Months

• Change from baseline in platelet count in transfusion dependent and transfusion independent patients

  Baseline, 30 Months

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

  Baseline, 30 Months

Study Arms (5)

Arm 1: MBG453 single agent

EXPERIMENTAL

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

Drug: MBG453

Arm 2: NIS793 single agent

EXPERIMENTAL

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

Drug: NIS793

Arm 3: canakinumab single agent

EXPERIMENTAL

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

Drug: canakinumab

Arm 4: MBG453 + NIS793 combination

EXPERIMENTAL

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

Drug: MBG453; Drug: NIS793

Arm 5: MBG453 + canakinumab combination

EXPERIMENTAL

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

Drug: MBG453; Drug: canakinumab

Interventions

MBG453 DRUG

Anti-TIM3 monoclonal antibody

Also known as: sabatolimab

Arm 1: MBG453 single agent; Arm 4: MBG453 + NIS793 combination; Arm 5: MBG453 + canakinumab combination

NIS793 DRUG

Anti-TGF-β monoclonal antibody

Arm 2: NIS793 single agent; Arm 4: MBG453 + NIS793 combination

canakinumab DRUG

Anti-IL-1β monoclonal antibody

Also known as: ACZ885

Arm 3: canakinumab single agent; Arm 5: MBG453 + canakinumab combination

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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 -

You may not qualify if:

• 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

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (13)

City Of Hope National Med Center Oncology

Duarte, California, 91010, United States

Location

H Lee Moffitt Cancer Center and Research Institute

Tampa, Florida, 33612, United States

Location

Massachusetts General Hospital .

Boston, Massachusetts, 02114, United States

Location

The Ohio State University Wexner Medical Center .

Columbus, Ohio, 43210, United States

Location

MD Anderson Cancer Center/University of Texas MD Anderson

Houston, Texas, 77030, United States

Location

Novartis Investigative Site

Prahran, Victoria, 3181, Australia

Location

Novartis Investigative Site

Tel Aviv, 6423906, Israel

Location

Novartis Investigative Site

Milan, MI, 20162, Italy

Location

Novartis Investigative Site

Singapore, 119228, Singapore

Location

Novartis Investigative Site

Singapore, 169608, Singapore

Location

Novartis Investigative Site

Seoul, 03080, South Korea

Location

Novartis Investigative Site

Salamanca, Castille and León, 37007, Spain

Location

Novartis Investigative Site

Barcelona, Catalonia, 08035, Spain

Location

Related Links

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

MeSH Terms

Conditions

Myelodysplastic Syndromes

Interventions

sabatolimab; NIS-793; canakinumab

Condition Hierarchy (Ancestors)

Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 9, 2021
• First Posted: March 23, 2021
• Study Start: June 18, 2021
• Primary Completion: April 19, 2024
• Study Completion: April 19, 2024
• Last Updated: October 10, 2025

Record last verified: 2025-10

Data Sharing

• IPD Sharing: Will not share

Locations

IT (1); SG (2); KR (1); ES (2); IL (1); US (5); AU (1)