A Study of MBG453 in Combination With Hypomethylating Agents in Subjects With IPSS-R Intermediate, High or Very High Risk Myelodysplastic Syndrome (MDS).

NCT ID: NCT03946670

Last Updated: 2026-01-13

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 127 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-06-04
• Study Completion Date: 2024-07-15

Brief Summary

This Phase II was a multicenter, randomized, two-arm parallel-group, double-blind, placebo-controlled study of MBG453 or placebo added to hypomethylating agents (azacitidine or decitabine) in adult subjects with IPSS-R intermediate, high or very high risk myelodysplastic syndrome (MDS) not eligible for Hematopoietic Stem Cell Transplant (HSCT) or intensive chemotherapy.

Detailed Description

The 2 primary objectives were as follows:

To determine if MBG453 combined with standard HMA therapy improved complete remission in subjects with intermediate, high, or very high risk MDS.

To determine if MBG453 combined with standard HMA therapy improved progression free survival (PFS) in subjects with intermediate, high or very high risk MDS.

This Phase II study was a multicenter, randomized, two-arm parallel-group, double-blind, placebo-controlled study of MBG453 or placebo added to hypomethylating agents (azacitidine or decitabine, as per investigators' choice based on local standard of care (SOC)) in adult subjects with IPSS-R intermediate, high or very high risk MDS not eligible for HSCT or intensive chemotherapy. A total of 127 subjects were randomized in a 1:1 ratio to treatment arms as follows:

• MBG453 400 mg IV Q2W and decitabine or azacitidine
• Placebo IV Q2W and decitabine or azacitidine

The randomization was stratified by 2 stratification factors: a) HMA (decitabine or azacitidine) selected by the investigator as per the local SOC and b) IPSS-R prognostic risk categories (intermediate, high or very high) at randomization. Crossover between treatment arms was not permitted at any time during the study.

Conditions

Myelodysplastic Syndromes

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

MBG453 + hypomethylating agents

Patients are taking MBG453 plus hypomethylating agents

Group Type: EXPERIMENTAL

MBG453

Intervention Type: DRUG

MBG453 is being administered i.v.

Hypomethylating agents

Intervention Type: DRUG

Decitabine is being administered i.v. Azacitidine is being administered i.v or s.c.

Placebo + hypomethylating agents

Patients are taking placebo plus hypomethylating agents

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Placebo is being administered i.v.

Hypomethylating agents

Intervention Type: DRUG

Decitabine is being administered i.v. Azacitidine is being administered i.v or s.c.

Interventions

MBG453

MBG453 is being administered i.v.

Intervention Type: DRUG

Placebo

Placebo is being administered i.v.

Intervention Type: DRUG

Hypomethylating agents

Decitabine is being administered i.v. Azacitidine is being administered i.v or s.c.

Intervention Type: DRUG

Other Intervention Names

Sabatolimab

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) 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):

• Very high
• High
• Intermediate with at least ≥ 5% bone marrow blast
• Not eligible at the time of screening, for intensive chemotherapy according to the investigator, based on local standard medical practice and institutional guidelines for treatment decisions
• Not eligible at the time of screening, for hematopoietic stem-cell transplantation (HSCT) according to the investigator, based on local standard medical practice and institutional guidelines for treatment decisions.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2

Exclusion Criteria

• Prior exposure to TIM-3 directed therapy at any time. Prior therapy with immune check point inhibitors (e.g. anti-CTLA4, anti-PD-1, anti-PD-L1, or anti-PD-L2), cancer vaccines are allowed except if the drug was administered within 4 months prior to randomization.
• Previous first-line treatment for higher risk MDS with chemotherapy or any other antineoplastic agents including lenalidomide and hypomethylating agent (HMAs) such as decitabine or azacitidine.
• History of severe hypersensitivity reactions to any ingredient of the study treatment (azacitidine, decitabine or MGB453) or their excipients, or to monoclonal antibodies (mAbs).
• Currently using or used within 14 days prior to randomization 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.
• Investigational treatment for MDS received within 4 weeks prior to randomization. In case of a checkpoint inhibitor: 4 months minimum prior to randomization interval is necessary to allow enrollment.
• Active autoimmune disease requiring systemic therapy (e.g.corticosteroids).
• Live vaccine administered within 30 Days prior to randomization.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 100 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

City Of Hope National Med Center

Duarte, California, United States

City of Hope National Medical Center Medical Oncology & Therapeutic

Duarte, California, United States

Yale University School Of Medicine

New Haven, Connecticut, United States

Dana Farber Cancer Institute

Boston, Massachusetts, United States

The Cancer Institute of New Jersey

New Brunswick, New Jersey, United States

Ohio State Comprehensive Cancer Center James Cancer Hospital

Columbus, Ohio, United States

Mary Crowley Cancer Research

Dallas, Texas, United States

Novartis Investigative Site

Vienna, , Austria

Novartis Investigative Site

Brasschaat, , Belgium

Novartis Investigative Site

Leuven, , Belgium

Novartis Investigative Site

Toronto, Ontario, Canada

Novartis Investigative Site

Québec, Quebec, Canada

Novartis Investigative Site

Brno, , Czechia

Novartis Investigative Site

Prague, , Czechia

Novartis Investigative Site

Toulouse, , France

Novartis Investigative Site

Leipzig, Saxony, Germany

Novartis Investigative Site

Berlin, , Germany

Novartis Investigative Site

Alexandroupoli, , Greece

Novartis Investigative Site

Larissa, , Greece

Novartis Investigative Site

Pátrai, , Greece

Novartis Investigative Site

Hong Kong, , Hong Kong

Novartis Investigative Site

Debrecen, Hajdu Bihar Megye, Hungary

Novartis Investigative Site

Nyíregyháza, , Hungary

Novartis Investigative Site

Florence, FI, Italy

Novartis Investigative Site

Milan, MI, Italy

Novartis Investigative Site

Rozzano, MI, Italy

Novartis Investigative Site

Reggio Calabria, RC, Italy

Novartis Investigative Site

Roma, RM, Italy

Novartis Investigative Site

Fukuoka, Fukuoka, Japan

Novartis Investigative Site

Fukushima, Fukushima, Japan

Novartis Investigative Site

Isehara, Kanagawa, Japan

Novartis Investigative Site

Kumamoto, Kumamoto, Japan

Novartis Investigative Site

Sendai, Miyagi, Japan

Novartis Investigative Site

Nagasaki, Nagasaki, Japan

Novartis Investigative Site

Bunkyo Ku, Tokyo, Japan

Novartis Investigative Site

Gifu, , Japan

Novartis Investigative Site

Osaka, , Japan

Novartis Investigative Site

Seoul, Korea, South Korea

Novartis Investigative Site

Seoul, , South Korea

Novartis Investigative Site

L'Hospitalet de Llobregat, Barcelona, Spain

Novartis Investigative Site

Santander, Cantabria, Spain

Novartis Investigative Site

Málaga, , Spain

Novartis Investigative Site

Kaohsiung City, , Taiwan

Novartis Investigative Site

Taipei, , Taiwan

Novartis Investigative Site

Samsun, Atakum, Turkey (Türkiye)

Novartis Investigative Site

Köseköy, Kocaeli, Turkey (Türkiye)

Novartis Investigative Site

Izmir, , Turkey (Türkiye)

Novartis Investigative Site

Manchester, , United Kingdom

Countries

United States; Austria; Belgium; Canada; Czechia; France; Germany; Greece; Hong Kong; Hungary; Italy; Japan; South Korea; Spain; Taiwan; Turkey (Türkiye); United Kingdom

References

Zeidan AM, Ando K, Rauzy O, Turgut M, Wang MC, Cairoli R, Hou HA, Kwong YL, Arnan M, Meers S, Pullarkat V, Santini V, Malek K, Kiertsman F, Niolat J, Ramos PM, Menssen HD, Fenaux P, Miyazaki Y, Platzbecker U. Sabatolimab plus hypomethylating agents in previously untreated patients with higher-risk myelodysplastic syndromes (STIMULUS-MDS1): a randomised, double-blind, placebo-controlled, phase 2 trial. Lancet Haematol. 2024 Jan;11(1):e38-e50. doi: 10.1016/S2352-3026(23)00333-2. Epub 2023 Dec 5.

Reference Type: DERIVED

PMID: 38065203 (View on PubMed)

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=2703

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

Other Identifiers

2018-004479-11

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

CMBG453B12201

Identifier Type: -

Identifier Source: org_study_id