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

Key inclusion criteria:

1. Signed informed consent was 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) primary or secondary based on 2016 WHO classification by Investigator assessment with one of the following prognostic risk categories, based on the International Prognostic Scoring System (IPSS-R).. Note: MDS diagnosis history were recorded in the CRF:

• Very high (> 6 points)

• High (> 4.5 to ≤ 6 points)

• Intermediate (> 3 to ≤ 4.5 points)

4. Not suitable at the time of Screening for immediate myeloablative/chemotherapy or HSCT based on Investigator assessment of age, comorbidities, local guidelines, institutional practice (any or all of these).

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

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

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

8. Estimated glomerular filtration rate ≥ 30 mL/min/1.73 m2 (estimation based on modification of diet in renal disease formula, by local laboratory).

9. Patient was able to communicate with the Investigator and had the ability to comply with the requirements of the study procedures.

Key exclusion criteria

1. 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 were allowed only if the last dose of the drug was administered more than 4 months prior to enrollment.

2. Previous treatment for intermediate, high or very high risk MDS (based on IPSS-R) with chemotherapy or other antineoplastic agents including lenalidomide and hypomethylating agent (HMAs) such as decitabine or INQOVI (oral decitabine) or azacitidine (patients who had up to 1 cycle of HMAs were included). However, previous treatment with hydroxyurea was permitted.

3. Diagnosis of acute myeloid leukemia (AML) including acute promyelocytic leukemia and extra-medullary acute myeloid leukemia based on WHO 2016 classification.

4. Diagnosis of Chronic myelomonocytic leukemia (CMML), or primary or secondary myelofibrosis based on 2016 WHO classification.

5. History of organ transplant or allogenic HSCT.

6. Patients with prior malignancy, except:

7. Patients with history of lower risk Myelodysplastic syndrome (MDS) treated by supportive care (e.g., growth factors, transforming growth factor- beta agents) or untreated were eligible.

8. Patients with history of lower risk MDS who were treated adequately with lenalidomide and then failed were eligible.

9. Patients with history of adequately treated malignancy for which no anticancer systemic therapy (namely chemotherapy, radiotherapy or surgery) was ongoing or required during the course of the study. Patients who were receiving adjuvant therapy such as hormone therapy were eligible.

10. Patients with MDS based on 2016 WHO classification with revised International Prognostic Scoring System (IPSS-R) ≤ 3.