A Study of MBG453 in Combination With Hypomethylating Agents in Subjects With IPSS-R Intermediate, High or Very High Risk Myelodysplastic Syndrome (MDS).
Condition: Myelodysplastic Syndromes
MeSH terms: Preleukemia; Myelodysplastic Syndromes; Syndrome
Intervention: MBG453; Placebo; Hypomethylating agents
Intervention description: MBG453 is being administered i.v.; Placebo is being administered i.v.; Decitabine is being administered i.v. Azacitidine is being administered i.v or s.c.
Phase: Phase 2
Study type: Interventional
Primary purpose: Supportive Care
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Enrollment: 127.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Sabatolimab; Placebo; Phase II; MBG453; TIM-3; decitabine; azacitidine; myelodysplastic syndrome (MDS)

Summary:

      This Phase II is a multicenter, randomized, two-arm parallel-group, double-blind,
      placebo-controlled study of MBG453 or placebo added to hypomethylating agents (azacitidine or
      decitabine) in adult subjects with IPSS-R intermediate, high or very high risk
      myelodysplastic syndrome (MDS) not eligible for Hematopoietic Stem Cell Transplant (HSCT) or
      intensive chemotherapy.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Signed informed consent must be obtained prior to participation in the study.

          2. Age ≥ 18 years at the date of signing the informed consent form (ICF)

          3. Morphologically confirmed diagnosis of a myelodysplastic syndrome (MDS) based on 2016
             WHO classification (Arber et al 2016) by investigator assessment with one of the
             following Prognostic Risk Categories, based on the International Prognostic Scoring
             System (IPSS-R):

               -  Very high

               -  High

               -  Intermediate with at least ≥ 5% bone marrow blast

          4. Not eligible at the time of screening, for intensive chemotherapy according to the
             investigator, based on local standard medical practice and institutional guidelines
             for treatment decisions

          5. Not eligible at the time of screening, for hematopoietic stem-cell transplantation
             (HSCT) according to the investigator, based on local standard medical practice and
             institutional guidelines for treatment decisions.

          6. Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2

        Exclusion Criteria:

          1. Prior exposure to TIM-3 directed therapy at any time. Prior therapy with immune check
             point inhibitors (e.g. anti-CTLA4, anti-PD-1, anti-PD-L1, or anti-PD-L2), cancer
             vaccines are allowed except if the drug was administered within 4 months prior to
             randomization.

          2. Previous first-line treatment for higher risk MDS with chemotherapy or any other
             antineoplastic agents including lenalidomide and hypomethylating agent (HMAs) such as
             decitabine or azacitidine.

          3. History of severe hypersensitivity reactions to any ingredient of the study treatment
             (azacitidine, decitabine or MGB453) or their excipients, or to monoclonal antibodies
             (mAbs).

          4. Currently using or used within 14 days prior to randomization 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.

          5. Investigational treatment for MDS received within 4 weeks prior to randomization. In
             case of a checkpoint inhibitor: 4 months minimum prior to randomization interval is
             necessary to allow enrollment.

          6. Active autoimmune disease requiring systemic therapy (e.g.corticosteroids).

          7. Live vaccine administered within 30 Days prior to randomization.

        Other protocol-defined Inclusion/Exclusion may apply.