MDS
Conditions
Interventions
Active agent arm: MBG453 400 mg Q2W i.v. plus Aza 75 mg/m2 i.v. or s.c.
Pracebo arm: Placebo 400 mg Q2W i.v. plus Aza 75 mg/m2 i.v. or s.c.
Sponsors
Novartis Pharma. K.K.
Eligibility
Sex/Gender
All
Inclusion 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 (IPSSR): -Very high (> 6 points) -High (> 4.5-6 points) -Intermediate (> 3-4.5 points): a subject determined to be in the Intermediate Prognostic Risk Category is only allowable in the setting of => 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 decision 5. Not eligible at the time of screening, for allogeneic stem-cell transplantation (HSCT) according to the investigator, based on local medical practice and institutional guidelines for treatment decisions 6. Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2
Exclusion criteria
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 intermediate, high or very high risk myelodysplastic syndromes (based on IPSS-R) 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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Efficacy -To determine if MBG453 combined with standard HMA therapy improves complete remission in subjects with intermediate, high, or very high risk MDS. -To determine if MBG453 combined with standard HMA therapy improves PFS in subjects with intermediate, high or very high risk MDS. | — |
Countries
Asia except Japan, Europe, Japan, North America, South America
Contacts
Public ContactKyosuke Yamauchi
Novartis Pharma. K.K.
Outcome results
None listed