Study Description
Main objective of this study is to describe and evaluate safety and efficacy of MBG453 (sabatolimab) in combination with FDA approved HMAs of investigator's choice (IV Decitabine or Azacitidine /SC Azacitidine /Oral Decitabine (cedazuridine combination (INQOVI))
This is a single-arm, non- randomized, open label, phase II multi-center study of intravenous MBG453 (sabatolimab) added to FDA approved Hypomethylating agents of investigator's choice (IV/SC/ Oral) in adult participants with intermediate, high or very high risk myelodysplastic syndrome (MDS) as per IPSS-R criteria.
There are three separate periods of this study:
Screening period (signing of written informed consent through Day 1);
Core phase for 24 months (with post treatment safety follow-up monitoring for adverse events (AEs) for 30 days following the last dose of azacitidine or decitabine or INQOVI (oral decitabine), or 150 days following the last dose of MBG453 (sabatolimab), whichever is later);
Extension phase for efficacy and/or survival status (up to 36 months from last patient enrolling) (with post treatment safety follow-up monitoring for adverse events (AEs) for 30 days following the last dose of azacitidine or decitabine or INQOVI (oral decitabine), or 150 days following the last dose of MBG453 (sabatolimab), whichever is later).
Interventions
Azacitidine
Decitabine
INQOVI (oral decitabine)
MBG453
Eligibility Criteria
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 or secondary based on 2016 WHO classification (Arber et al 2016) by investigator assessment with one of the following Prognostic Risk Categories, based on the International Prognostic Scoring System (IPSS-R). Note: MDS diagnosis history will be 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 or hematopoietic 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 on Modification of Diet in Renal Disease (MDRD) formula, by local laboratory).
Patient is able to communicate with the investigator and has the ability to comply with the requirements of the study procedures.
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 are allowed only if the last dose of the drug was administered more than 4 months prior to enrollment.
Previous treatment for intermediate, high or very high risk myelodysplastic syndromes (based on IPSS-R) with chemotherapy or other antineoplastic agents including lenalidomide and hypomethylating agent (HMAs) such as decitabine or azacitidine or INQOVI (oral decitabine) (patients who had up to 1 cycle of HMAs can be included). However, previous treatment with hydroxyurea is permitted.
Diagnosis of acute myeloid leukemia (AML) including acute promyelocytic leukemia and extra-medullary acute myeloid leukemia based on WHO 2016 classification (Arber et al 2016).
Diagnosis of Chronic myelomonocytic leukemia (CMML), or primary or secondary myelofibrosis based on 2016 WHO classification (Arber et al 2016).
History of organ transplant or allogenic hematopoietic stem cell transplant
Participants with prior malignancy, except:
Participants with history of lower risk MDS treated by supportive care (e.g. growth factors, TGF-beta agents) or untreated are eligible
Participants with history of lower risk MDS who were treated adequately with lenalidomide and then failed are eligible
Participants with history of adequately treated malignancy for which no anticancer systemic therapy (namely chemotherapy, radiotherapy or surgery) is ongoing or required during the course of the study. Participants who are receiving 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
Study Location
Illinois Cancer Care P.C. .
Recruiting
Peoria,Leonard Klein,61615-7828 - Illinois,United States
Ironwood Cancer and Research Centers
Recruiting
Chandler,(480-855-2225) -- Mikhail I Shtivelband,85224 - Arizona,United States
Alliance Cancer Specialists USO
Recruiting
Horsham,Joseph Potz,19044 - Pennsylvania,United States
Messino Cancer Centers
Recruiting
Asheville,Christopher Chay,28806 - North Carolina,United States
Arizona Oncology Associates .
Recruiting
Tucson,Sudhir Manda,85745 - Arizona,United States
Texas Oncology-Baylor USO
Recruiting
Dallas,Moshe Levy,75246 - Texas,United States
Arizona Oncology Associates Arizona Oncology Assoc PC
Recruiting
Phoenix,(520-877-9096) -- Sudhir Manda,85016 - Arizona,United States
Worldwide Contacts
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