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

NCT03946670 | Terminated Phase 2 Results DMC FDA Drug

• 2 other identifiers: CMBG453B122012018-004479-11
• Study Type: interventional
• Target: 127
• Locations: 17 countries
• Sites: 48

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.

Conditions

Myelodysplastic Syndromes

Keywords

Sabatolimab; Placebo; Phase II; MBG453; TIM-3; decitabine; azacitidine; myelodysplastic syndrome (MDS)

Outcome Measures

Primary Outcomes (2)

• Complete Remission (CR) Rate

  CR: where the Bone marrow: ≤ 5% blasts with normal maturation of all cell lineages and Peripheral blood: where Hgb ≥ 10 g/dL AND Platelets ≥ 100\*109/L AND Neutrophils ≥ 1.0\*109/L AND Peripheral blasts 0%. Modified response criteria According to International Working Group (IWG) and as per World Health Organization (WHO) criteria for Myelodysplastic syndromes (MDS) as per investigator assessment.

  average of 7 months

• Progression Free Survival (PFS)

  PFS is defined as time from randomization to disease progression (including transformation to acute leukemia per WHO 2016 classification), relapse from CR according to IWG-MDS or death due to any cause, whichever occurs first, as per investigator assessment.

  approx. 32 months

Secondary Outcomes (13)

• Progression Free Survival (PFS) - Final PFS

  approx. 48 months

• Overall Survival (OS)

  approx. 48 months

• Event-free Survival (EFS)

  approx. 48 months

• Leukemia-free Survival (LFS)

  approx. 48 months

• Response Rate of Complete Remission (CR)/Marrow Complete Remission (mCR)/Partial Remission (PR)/Hematopoietic Improvement (HI))

  approx. 32 months

Study Arms (2)

MBG453 + hypomethylating agents

EXPERIMENTAL

Patients are taking MBG453 plus hypomethylating agents

Drug: MBG453; Drug: Hypomethylating agents

Placebo + hypomethylating agents

PLACEBO COMPARATOR

Patients are taking placebo plus hypomethylating agents

Drug: Placebo; Drug: Hypomethylating agents

Interventions

MBG453 DRUG

MBG453 is being administered i.v.

Also known as: Sabatolimab

MBG453 + hypomethylating agents

Placebo DRUG

Placebo is being administered i.v.

Placebo + hypomethylating agents

Hypomethylating agents DRUG

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

MBG453 + hypomethylating agents; Placebo + hypomethylating agents

Eligibility Criteria

• Age: 18 Years - 100 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (48)

City Of Hope National Med Center

Duarte, California, 91010, United States

Location

City of Hope National Medical Center Medical Oncology & Therapeutic

Duarte, California, 91010, United States

Location

Yale University School Of Medicine

New Haven, Connecticut, 06520, United States

Location

Dana Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

The Cancer Institute of New Jersey

New Brunswick, New Jersey, 08901, United States

Location

Ohio State Comprehensive Cancer Center James Cancer Hospital

Columbus, Ohio, 73210, United States

Location

Mary Crowley Cancer Research

Dallas, Texas, 75251, United States

Location

Novartis Investigative Site

Vienna, 1140, Austria

Location

Novartis Investigative Site

Brasschaat, 2930, Belgium

Location

Novartis Investigative Site

Leuven, 3000, Belgium

Location

Novartis Investigative Site

Toronto, Ontario, M5G 2M9, Canada

Location

Novartis Investigative Site

Québec, Quebec, G1J 1Z4, Canada

Location

Novartis Investigative Site

Brno, 625 00, Czechia

Location

Novartis Investigative Site

Prague, 128 08, Czechia

Location

Novartis Investigative Site

Toulouse, 31059, France

Location

Novartis Investigative Site

Leipzig, Saxony, 04103, Germany

Location

Novartis Investigative Site

Berlin, 13353, Germany

Location

Novartis Investigative Site

Alexandroupoli, 681 00, Greece

Location

Novartis Investigative Site

Larissa, 411 10, Greece

Location

Novartis Investigative Site

Pátrai, 265 04, Greece

Location

Novartis Investigative Site

Hong Kong, Hong Kong

Location

Novartis Investigative Site

Debrecen, Hajdu Bihar Megye, 4032, Hungary

Location

Novartis Investigative Site

Nyíregyháza, 4400, Hungary

Location

Novartis Investigative Site

Florence, FI, 50134, Italy

Location

Novartis Investigative Site

Milan, MI, 20162, Italy

Location

Novartis Investigative Site

Rozzano, MI, 20089, Italy

Location

Novartis Investigative Site

Reggio Calabria, RC, 89124, Italy

Location

Novartis Investigative Site

Roma, RM, 00133, Italy

Location

Novartis Investigative Site

Fukuoka, Fukuoka, 812-8582, Japan

Location

Novartis Investigative Site

Fukushima, Fukushima, 960 1295, Japan

Location

Novartis Investigative Site

Isehara, Kanagawa, 259-1193, Japan

Location

Novartis Investigative Site

Kumamoto, Kumamoto, 860-0008, Japan

Location

Novartis Investigative Site

Sendai, Miyagi, 983 8520, Japan

Location

Novartis Investigative Site

Nagasaki, Nagasaki, 852-8501, Japan

Location

Novartis Investigative Site

Bunkyo Ku, Tokyo, 113-8677, Japan

Location

Novartis Investigative Site

Gifu, 500 8513, Japan

Location

Novartis Investigative Site

Osaka, 545-8586, Japan

Location

Novartis Investigative Site

Seoul, Korea, 03080, South Korea

Location

Novartis Investigative Site

Seoul, 06351, South Korea

Location

Novartis Investigative Site

L'Hospitalet de Llobregat, Barcelona, 08907, Spain

Location

Novartis Investigative Site

Santander, Cantabria, 39008, Spain

Location

Novartis Investigative Site

Málaga, 29010, Spain

Location

Novartis Investigative Site

Kaohsiung City, 83301, Taiwan

Location

Novartis Investigative Site

Taipei, 10002, Taiwan

Location

Novartis Investigative Site

Samsun, Atakum, 55200, Turkey (Türkiye)

Location

Novartis Investigative Site

Köseköy, Kocaeli, 41380, Turkey (Türkiye)

Location

Novartis Investigative Site

Izmir, 35100, Turkey (Türkiye)

Location

Novartis Investigative Site

Manchester, M20 2BX, United Kingdom

Location

Related Publications (1)

• 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.

  PMID: 38065203 DERIVED

Related Links

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

MeSH Terms

Conditions

Myelodysplastic Syndromes

Interventions

sabatolimab

Condition Hierarchy (Ancestors)

Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases

Limitations and Caveats

A total of 127 subjects were randomized (65 to sabatolimab (S)+HMA arm, 62 to placebo (P)+HMA arm. However, only 125 subjects were treated (64 in S+HMA arm, 61 in P+HMA arm). Two subjects in S+HMA arm received only HMA, and, as a result, were reported in P+HMA arm in the safety dataset. Therefore, the safety dataset included a total of 62 subjects in the S+HMA arm \& 63 subjects in the P+HMA arm.

Results Point of Contact

• Title: Study Director
• Organization: Novartis Pharmaceuticals

novartis.email@novartis.com

862-778-8300

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 8, 2019
• First Posted: May 13, 2019
• Study Start: June 4, 2019
• Primary Completion: April 26, 2022
• Study Completion: July 15, 2024
• Last Updated: January 13, 2026
• Results First Posted: July 7, 2023

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will share
• Access Criteria: Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent expert panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations. This trial data is currently available according to the process described on www.clinicalstudydatarequest.com.

Locations

FR (1); AU (1); TU (3); GB (1); BE (2); CZ (2); DE (2); TW (2); ES (3); CA (2); US (7); IT (5); GR (3); HU (2); KR (2); HK (1); JP (9)