adult subjects with intermediate, high or very high risk (per IPSS-R prognostic risk categories) myelodysplastic syndrome or with Chronic Myelomonocytic Leukemia - 2 (CMML-2) MedDRA version: 20.0 Level: HLT Classification code 10028536 Term: Myelodysplastic syndromes System Organ Class: 100000004851 MedDRA version: 21.0 Level: PT Classification code 10009018 Term: Chronic myelomonocytic leukaemia System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Product Name: sabatolimab
Product Code: MBG453
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: sabatolimab
Current Sponsor code: MBG453
Other descriptive name: MBG453
C
Sponsors
Novartis Pharma AG
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Key inclusion criteria: • Signed informed consent must be obtained prior to participation in the study • Age = 18 years at the date of signing the informed consent form (ICF) • Morphologically confirmed diagnosis of myelodysplastic syndrome (MDS) based on WHO 2016 classification (Arber et al 2016) by local investigator assessment with one of the following Prognostic Risk Categories, based on the revised International Prognostic Scoring System (IPSS-R): • Very high (> 6 points) • High (> 4.5 - = 6 points) • Intermediate (> 3 - = 4.5 points) Or Morphologically confirmed diagnosis of Chronic Myelomonocytic Leukemia -2 based on WHO 2016 classification (Arber et al 2016- persistant PB monocytosis = 1 x109/L and monocytes accounting for = 10% of the WBC differential count)) by local investigator assessment with WBC =65 years) yes F.1.3.1 Number of subjects for this age range 350
Exclusion criteria
Exclusion criteria: Key exclusion criteria: • Prior exposure to TIM-3 directed therapy at any time. Prior therapy with immune checkpoint inhibitors (e.g, anti-CTLA4, anti-PD-1, anti-PD-L1, or anti-PD-L2), cancer vaccines is allowed except if the drug was administered within 4 months prior to randomization • Previous first-line treatment for intermediate, high, very high risk myelodysplastic syndromes (based on IPSS-R) or CMML-2 with any antineoplastic agents including for example chemotherapy, lenalidomide and hypomethylating agents (HMAs) such as decitabine or azacitidine. However, previous treatment with hydroxyurea or leukopheresis to reduce WBC count is allowed prior to randomization. • Investigational treatment received within 4 weeks or 5 half-lives of this investigational treatment, whatever is longer, prior to randomization. In case of a checkpoint inhibitor: a minimal interval of 4 months prior to randomization is necessary to allow randomization. • Subjects with Myelodysplastic syndrome (MDS) based on 2016 WHO classification (Arber et al 2016) with revised International Prognostic Scoring System (IPSS-R) = 3 • Diagnosis of acute myeloid leukemia (AML) including acute promyelocytic leukemia and extra-medullary acute myeloid leukemia, primary or secondary myelofibrosis based on WHO 2016 classification (Arber et al 2016) • Diagnosis of therapy related myeloid neoplasms based on WHO 2016 classification (Arber et al 2016) • History of organ or allogeneic hematopoietic stem cell transplant Please refer to protocol for further details and any additional exclusion criteria.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To compare overall survival (OS) in the MBG453 plus azacitidine arm versus placebo plus azacitidine arm;Secondary Objective: Key Secondary: 1:compare time to definitive deterioration of fatigue in the MBG453 plus azacitidine arm versus placebo plus azacitidine arm 2: compare RBC transfusion-free intervals in the MBG453 plus azacitidine arm vs placebo plus azacitidine arm 3: compare improvement of fatigue in the MBG453 plus azacitidine arm vs placebo plus azacitidine arm 4: compare improvement of physical functioning in the MBG453 plus azacitidine arm vs placebo plus azacitidine arm 5: compare improvement of emotional functioning in the MBG453 plus azacitidine arm vs placebo plus azacitidine arm Other: •assess response rate in each treatment arm •assess PFS in each treatment arm •assess leukemia-free survival in each treatment arm •assess safety profile of MBG453 when given in combination with azacitidine •assess improvement in RBC/Platelets transfusion independence in each treatment arm •characterize the PK of MBG453 •evaluate immunogenicity of MBG453 •assess overall QoL in each treatment arm;Primary end point(s): OS is the time from randomization until death due to any cause. If the subject is not known to have died, then OS will be censored at the latest date the subject was known to be alive (on or before cut-off date). ;Timepoint(s) of evaluation of this end point: Estimated at 28 months and 33 months after first patient randomized and up to 5 years after the first patient randomized | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Key secondary endpoints: 1. Time from randomization to at least 3 points worsening from baseline in FACIT-fatigue scores with no subsequent improvement above this threshold or death due to any cause, whichever occurs first 2. Cumulative time of intervals with no evidence of RBC transfusion for at least 8 weeks at any point after randomization 3. Percent of subjects with at least 3 point confirmed improvement from baseline in FACIT-fatigue scores 4. Percent of subjects with at least 10 point confirmed improvement from baseline in physical functioning using EORTC QLQ-C30 5. Percent of subjects with at least 10 point confirmed improvement from baseline in emotional functioning using EORTC QLQ-C30 Other endpoints: a) Percentage of CR/mCR/PR/HI according to IWG-MDS as per investigator assessment; Percentage of SD according to IWG-MDS as per investigator assessment b) Time from randomization to disease progression (including transformation to acute leukemia per WHO 2016 classification), relapse from complete remission (CR) according to IWG-MDS or death due to any cause, whichever occurs first, as per investigator assessment c) Time from randomization to = 20% blasts in bone marrow/peripheral blood (per WHO 2016 classification) or diagnosis of extramedullary acute leukemia, or death due to any cause d) Incidence and severity of AEs and SAEs, changes in laboratory values and vital signs (per CTCAE version 5) e) Number and percent of transfusion dependent subjects at baseline who become RBC/platelets transfusion independent after randomization as per IWG-MDS criteria f) Serum concentrations and pharmacokinetic parameters for MBG453 g) Anti-drug Antibody (ADA) prevalence at baseline and ADA incidence on-treatment h) Change from baseline in EQ-5D-5L scores and VAS scores over time; Change from baseline to C12D1 of Global Health Status/QoL scores using EORTC QLQ-C30 ;Timepoint(s) of evaluation of this end point: 1&3 C3D1 & every 2 cycles | — |
Countries
Argentina, Australia, Austria, Belgium, Brazil, Canada, Chile, China, Colombia, Czechia, Czech Republic, Finland, France, Germany, Greece, India, Israel, Italy, Japan, Korea, Republic of, Lebanon, Lithuania, Malaysia, Mexico, Netherlands, Oman, Portugal, Russian Federation, Saudi Arabia, Singapore, Spain, Switzerland, Taiwan, Thailand, Turkey, United Kingdom, United States
Contacts
Public ContactClinical Trial Information Desk
Novartis Pharma AG
Outcome results
None listed