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

NCT ID: NCT04878432

Last Updated: 2025-10-16

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 39 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-03-17
• Study Completion Date: 2024-09-01

Brief Summary

The main objective of this study was to assess the safety profile of MBG453 (sabatolimab) in combination with FDA approved hypomethylating agents (HMAs) of investigator's choice (IV Decitabine or Azacitidine /SC Azacitidine /Oral Decitabine (cedazuridine combination (INQOVI))).

Detailed Description

This was a single arm, nonrandomized, open label, Phase II multicenter study of i.v sabatolimab added to FDA approved HMA agents of Investigator's choice (i.v/s.c/oral) in adult patients with intermediate, high or very high risk MDS as per IPSS-R criteria.

There were 4 separate periods of this study:

1. Screening period (signing of written informed consent through day of enrollment),

2. Core phase for up to 12 months,

3. Extension phase for efficacy and/or survival status (up to 12 months after the core phase),

4. Post-treatment safety follow-up period monitoring for AEs for 30 days following the last dose of azacitidine or decitabine or INQOVI (oral decitabine), or 150 days following the last dose of sabatolimab, whichever was later.

During the conduct of the study there were 2 updates to the Novartis development strategy for sabatolimab. Based on the results from the Phase II STIMULUS MDS-1 study, recruitment was halted for CMBG453B1US01 (STIMULUS MDS-US) on 30-Sep-2022. Novartis confirmed the decision to halt recruitment was not based on any safety findings or safety concerns. Patients who were on study treatment or in follow-up were continued as per the protocol. Furthermore, on 11-Jan-2024, all sabatolimab investigators were notified by Novartis that, based on decision taken in Dec-2023, that the sabatolimab development program (which included study CMBG453B1US01) would be terminated. After the decision was made to discontinue the sabatolimab development program, participants already enrolled in the CMBG453B1US01 study were prepared for closure; these close out activities took approximately 9 months. The actual last patient last visit date was 1 Sep 2024.

Conditions

Myelodysplastic Syndrome (MDS)

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

MBG453 (sabatolimab) + HMA

MBG453 (sabatolimab) + HMA of investigator's choice (IV Decitabine or Azacitidine /SC Azacitidine /Oral Decitabine (cedazuridine combination (INQOVI)))

Group Type: EXPERIMENTAL

MBG453

Intervention Type: DRUG

Solution for intravenous infusion

Azacitidine

Intervention Type: DRUG

Solution for subcutaneous injection or intravenous administration

Decitabine

Intervention Type: DRUG

Solution for intravenous administration

INQOVI (oral decitabine)

Intervention Type: DRUG

Tablet for oral administration

Interventions

MBG453

Solution for intravenous infusion

Intervention Type: DRUG

Azacitidine

Solution for subcutaneous injection or intravenous administration

Intervention Type: DRUG

Decitabine

Solution for intravenous administration

Intervention Type: DRUG

INQOVI (oral decitabine)

Tablet for oral administration

Intervention Type: DRUG

Other Intervention Names

sabatolimab

Eligibility Criteria

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.

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:

1. 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.

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

3. 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.

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 99 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Novartis Pharmaceuticals

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Novartis Pharmaceuticals

Role: STUDY_DIRECTOR

Novartis Pharmaceuticals

Locations

Mayo Clinic Arizona

Phoenix, Arizona, United States

Arizona Oncology Associates

Tucson, Arizona, United States

SCRI-Colorado Blood Cancer Institute

Denver, Colorado, United States

Yale University School Of Medicine

New Haven, Connecticut, United States

Advent Health Orlando

Orlando, Florida, United States

Uni of Massachusetts Medical Center

Worcester, Massachusetts, United States

University Of Michigan

Ann Arbor, Michigan, United States

Karmanos Cancer Institute

Detroit, Michigan, United States

Tisch Hospital NYU Langone

New York, New York, United States

Mount Sinai Medical Center

New York, New York, United States

Duke Cancer Institute

Durham, North Carolina, United States

University Hospitals Of Cleveland

Cleveland, Ohio, United States

Cleveland Clinic

Cleveland, Ohio, United States

Uni Of TX MD Anderson Cancer Cntr

Houston, Texas, United States

Texas Oncology San Antonio USO

San Antonio, Texas, United States

Countries

United States

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Related Links

https://www.novctrd.com/ctrdweb/patientsummary/patientsummaries?patientSummaryId=2688

A Plain Language Trial Summary is available on www.novctrd.com

Other Identifiers

CMBG453B1US01

Identifier Type: -

Identifier Source: org_study_id