Single-arm, Open Label, Phase II Study of MBG453 (Sabatolimab) Added to FDA Approved Hypomethylating Agents of Investigator's Choice (IV/SC/Oral) for Patients With Intermediate, High or Very High Risk Myelodysplastic Syndrome (MDS) as Per IPSS-R Criteria (US Multi-center) (STIMULUS MDS-US) STIMULUS MDS-US

What's the purpose of this trial?

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 trial is currently open and accepting patients.

What will happen during the trial?

You may be able to join this trial if you:

The following criteria is a partial list of reasons why patients may be eligible to participate in this clinical trial. Further evaluation with a medical professional is required.

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:

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 with lenalidomide and then failed are eligible
3. 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

Additional Trial Information

Phase 2

Enrollment: 90 patients (estimated)

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Published Results

Sabatolimab in Combination with Hypomethylating Agents (HMAs) Was Safe in Patients (Pts) with Intermediate-, High-, or Very-High-Risk Myelodysplastic Syndrome (MDS)

December 11, 2023

RESULTS: This interim analysis included 33 pts with intermediate-, high-, and very-high-risk MDS at the data cutoff of 6 months after cycle 1 day 1 of treatment with sabatolimab and an HMA. The median age was 69 years (range, 39-86). At data cutoff, 8 pts were in ongoing treatment, and 25 pts had discontinued the core phase. Reasons for discontinuation included new therapy for study indication (n=6), physician decision (n=6), pt decision (n=5), progressive disease (n=4), unsatisfactory therapeutic effect (n=2), adverse event (AE) (n=1), and death (n=1). Of those who discontinued study treatment, 6 pts were in ongoing evaluation in the extension phase and 3 pts were in ongoing evaluation in the post-treatment follow-up phase. The median duration (range) of exposure was 3.9 (0.92-5.91) months for sabatolimab and 4.2 (1.05-6.08) months for HMAs.

Among 33 pts evaluable for safety, most experienced all-grade and grade ≥3 AEs, AEs requiring additional therapy, and serious AEs (Figure). However, the most frequent (≥10%) grade ≥3 AEs were expected hematologic AEs, including febrile neutropenia (42.4%), anemia (39.4%), neutrophil count decrease (39.4%), and platelet count decrease (36.4%). Nonhematologic grades ≥3 AEs occurring in >1 pt included hypertension (18.2%), pneumonia (9.1%), hypoxia (6.1%), and fall (6.1%). Only 1 pt was reported with encephalopathy leading to treatment discontinuation, which was not attributed to study treatment. One pt had a fatal AE for which the cause was not identified but not thought to be related to study treatment by the investigator.

The best overall response results in up to 6 months of treatment were available for 22 pts. Marrow CR (mCR) with and without hematologic improvement (HI) was reported in 18.2% and 9.1%, respectively. Partial remission (PR) and stable disease (SD) with HI was reported in 4.5%, each. CR + mCR + PR was 31.8% (95% CI, 13.9%-54.9%), CR + PR + HI was 27.3% (95% CI, 10.7%-50.2%), and CR + mCR + PR + HI was 36.4% (95% CI, 17.2%-59.3%).

CONCLUSIONS: This interim analysis of the STIMULUS-MDS US study demonstrated that sabatolimab in combination with an oral, IV, or SC HMA was safe and well tolerated, with AEs consistent with previous reports for pts with MDS treated with HMAs. Response rates for the combination are preliminary, and more information will be provided with longer follow-ups.

Trial Links

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Trial Locations

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Ironwood Cancer & Research Centers - Chandler I

Chandler, AZ

Open and Accepting

Arizona Oncology Associates Arizona Oncology Assoc PC

Phoenix, AZ

Open and Accepting


Illinois CancerCare - Peoria

Peoria, IL

Open and Accepting


University of Massachusetts Medical School

Worcester, MA

Open and Accepting

North Carolina

Messino Cancer Centers

Asheville, NC

Open and Accepting



Alliance Cancer Specialist

Horsham, PA

Open and Accepting


Baylor Charles A. Sammons Cancer Center Baylor Scott & White Health

Dallas, TX

Open and Accepting
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