A randomized, double-blind, placebo-controlled phase III multi-center study of azacitidine with or without MBG453 for the treatment of patients with intermediate, high or very high risk myelodysplastic syndrome (MDS) as per IPSS-R, or Chronic Myelomonocytic Leukemia-2 (CMML-2)

• 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)
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
• Indication for azacitidine treatment according to the investigator, based on
local standard medical practice and institutional guidelines for treatment
decisions
• Not eligible at time of screening for intensive chemotherapy according to the
investigator, based on local standard medical practice and institutional
guidelines for treatment decisions decisions, including assessment of
individual clinical factors such as age, comorbidities and performance status
• Not eligible at time of screening for hematopoietic stem cell transplantation
according to the investigator, based on local standard medical practice and
institutional guidelines for treatment decisions including assessment of
individual clinical factors such as age, comorbidities, performance status, and
donor availability
• Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2
Please refer to protocol for further details and any additional inclusion
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 grade 2 or higher based on WHO 2016 classification (Arber et al
2016). Patients with myelofibrosis grade 1 must not be enrolled if they have
symptoms of concurrent myeloproliferative neoplasm
• 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.