STIMULUS MDS-US : Sabatolimab Added to HMA in Higher Risk MDS

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 a myelodysplastic syndrome (MDS) primary orsecondary based on 2016 WHO classification (Arber et al 2016) by investigatorassessment with one of the following Prognostic Risk Categories, based on theInternational Prognostic Scoring System (IPSS-R). Note: MDS diagnosis history willbe recorded in the CRF:

• Very high (> 6 points)

• High (> 4.5 - ≤ 6 points)

• Intermediate (> 3 - ≤ 4.5 points)

• Not suitable at the time of screening for immediate myeloablative/ chemotherapy orhematopoietic stem cell transplantation based on investigator assessment of age,comorbidities, local guidelines, institutional practice (any or all of these).

• Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2.

• AST and ALT ≤ 3 × upper limit of normal (ULN).

• Total bilirubin ≤ 2 × ULN (except in the setting of isolated Gilbert syndrome).

• Estimated Glomerular Filtration Rate (eGFR) ≥ 30 mL/min/1.73m2 (estimation based onModification of Diet in Renal Disease (MDRD) formula, by local laboratory).

• Patient is able to communicate with the investigator and has the ability to complywith the requirements of the study procedures.

Exclusion Criteria:

• Prior exposure to TIM-3 directed therapy at any time. Prior therapy with immunecheckpoint inhibitors (e.g. anti-CTLA4, anti-PD-1, anti-PD-L1, or anti-PD-L2),cancer vaccines are allowed only if the last dose of the drug was administered morethan 4 months prior to enrollment.

• Previous treatment for intermediate, high or very high risk myelodysplasticsyndromes (based on IPSS-R) with chemotherapy or other antineoplastic agentsincluding lenalidomide and hypomethylating agent (HMAs) such as decitabine orazacitidine or INQOVI (oral decitabine) (patients who had up to 1 cycle of HMAs canbe included). However, previous treatment with hydroxyurea is permitted.

• Diagnosis of acute myeloid leukemia (AML) including acute promyelocytic leukemia andextra-medullary acute myeloid leukemia based on WHO 2016 classification (Arber et al 2016).

• Diagnosis of Chronic myelomonocytic leukemia (CMML), or primary or secondarymyelofibrosis based on 2016 WHO classification (Arber et al 2016).

• History of organ transplant or allogenic hematopoietic stem cell transplant

• Participants with prior malignancy, except:

1. Participants with history of lower risk MDS treated by supportive care (e.g.growth factors, TGF-beta agents) or untreated are eligible

2. Participants with history of lower risk MDS who were treated adequately withlenalidomide and then failed are eligible

3. Participants with history of adequately treated malignancy for which noanticancer systemic therapy (namely chemotherapy, radiotherapy or surgery) isongoing or required during the course of the study. Participants who arereceiving adjuvant therapy such as hormone therapy are eligible.

• Participants with Myelodysplastic syndrome (MDS) based on 2016 WHO classification (Arber et al 2016) with revised International Prognostic Scoring System (IPSS-R) ≤ 3