A Study of Sabatolimab in Combination With Azacitidine and Venetoclax in High or Very High Risk MDS Participants

Recruitment & Eligibility

Status: Suspended

Sex: All

Target Recruitment: 3

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 myelodysplastic syndrome (MDS) based on 2016 WHO 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) (Greenberg et al 2012):
- Very high (> 6 points)
- High (> 4.5-6 points)
4- Not immediately eligible for hematopoietic stem-cell transplantation (HSCT) or intensive chemotherapy at the time of screening due to individual clinical factors such as age, comorbidities and performance status, donor availability (de Witte et al 2017)
5- Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2

Exclusion Criteria

1- Prior exposure to TIM-3 directed therapy or any BCL-2 inhibitor (including venetoclax) at any time
2- Prior therapy with immune check point inhibitors (e.g. anti-CTLA4, anti-PD-1, anti-PD-L1, or anti-PD-L2) or cancer vaccines is not allowed if the last dose of the drug was administered within 4 months prior to start of treatment
3- Previous first-line treatment for very high risk or high risk myelodysplastic syndromes (based on IPSS-R,Greenberg et al 2012 and Arber et al, 2016) with any antineoplastic agents, approved or investigational, including for example chemotherapy, lenalidomide and hypomethylating agents (HMAs) such as decitabine or azacitidine However, a one single cycle of HMAs treatment only started prior to enrollment is allowed.
4- Live vaccine administered within 30 days prior to start of treatment
5- Current use or use within 14 days prior to start of treatment 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
6- History of severe hypersensitivity reactions to any ingredient of study drug(s) (azacitidine, venetoclax or sabatolimab) or monoclonal antibodies (mAbs) and/or their excipients
7- Participants with Myelodysplastic syndrome (MDS) based on 2016 WHO classification (Arber et al, 2016) with revised International Prognostic Scoring System (IPSS-R) = 4.5

Study & Design

Study Type: Interventional

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
ame: Percentage of participants (receiving 800mg sabatolimab) achieving complete remission (CR) per investigator assessment;Timepoints: Throughout study completion, up to 3 years;Measure: This endpoint will assess Complete Remission (CR) Rate of participants from Cohort 2 of Part 1 and Part 2 according to Investigator assessment per modified IWG-MDS - Cheson 2006 criteria. CR is defined as follows: bone marrow blasts <=5%, hemoglobin level = 10 g/dL, platelets count = 10010^9/L, neutrophils count = 1.010^9/L, absence of blasts in peripheral blood.;Name: Incidence of dose limiting toxicities (DLTs) (Safety run-in patients only);Timepoints: From Cycle 1 Day 8 to end of Cycle 2 (Cycle = 28 Days);Measure: Assessment of tolerability of MBG in combination with venetoclax and azacitidine

Secondary Outcome Measures

Name	Time	Method

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