Study of Efficacy and Safety of MBG453 in Combination With Azacitidine in Subjects With Intermediate, High or Very High Risk Myelodysplastic Syndrome (MDS) as Per IPSS-R, or Chronic Myelomonocytic Leukemia-2 (CMML-2)

NCT04266301 | Terminated Phase 3 Results DMC FDA Drug

• 2 other identifiers: CMBG453B123012019-002089-11
• Study Type: interventional
• Target: 530
• Locations: 35 countries
• Sites: 146

Brief Summary

This was a Phase III multi-center, randomized, two-arm parallel-group, double-blind, placebo-controlled study of MBG453 or placebo added to azacitidine in adult participants with intermediate, high or very high-risk myelodysplastic syndrome (MDS) as per IPSS-R, or Chronic Myelomonocytic Leukemia-2 (CMML-2) who are not eligible for intensive chemotherapy or hematopoietic stem cell transplantation (HSCT) according to medical judgment by the investigator. The purpose of the current study was to assess clinical effects of MBG453 in combination with azacytidine in adult participants with IPSS-R intermediate, high, very high risk MDS and CMML-2.

Conditions

Myelodysplastic Syndromes; Leukemia, Myelomonocytic, Chronic

Keywords

MBG453; Phase III; TIM-3; azacitidine; myelodysplastic syndrome; MDS; chronic myelomonocytic leukemia; CMML-2; Sabatolimab; high or; very high risk myelodysplastic syndrome; Chronic Myelomonocytic Leukemia-2

Outcome Measures

Primary Outcomes (2)

• Overall Survival (OS) (Primary Efficacy Results)

  OS is the time from randomization until death due to any cause.

  up to approx. 39 months

• Overall Survival (OS) (Final Efficacy Results)

  OS is the time from randomization until death due to any cause.

  up to approx. 52 months

Secondary Outcomes (17)

• Key Secondary Endpoint 1: Time to Definitive Deterioration of Fatigue Using Functional Assessment of Cancer Therapy (FACIT)-Fatigue Score

  up to approx. 52 months

• Key Secondary Endpoint 2: Red Blood Cell (RBC) Annualized Transfusion Free Rate for Transfusion

  up to approx. 52 months

• Key Secondary Endpoint 3: Percentage of Participants With at Least 3 Point Confirmed Improvement From Baseline in FACIT-fatigue Scores

  up to approx. 52 months

• Key Secondary Endpoint 4: Percentage of Participants With at Least 10 Point Confirmed Improvement From Baseline in Physical Functioning Using European Organization for Research and Treatment of Cancer's Core Quality of Life Questionnaire (EORTC QLQ-C30)

  up to approx. 52 months

• Key Secondary Endpoint 5: Percentage of Participants With at Least 10 Point Confirmed Improvement From Baseline in Emotional Functioning Using EORTC-QLQ-C30

  up to approx. 52 months

Study Arms (2)

Sabatolimab (MBG453) + Azacitidine

EXPERIMENTAL

Participants received sabatolimab plus Azacitidine

Drug: Sabatolimab; Drug: Azacitidine

Placebo + Azacitidine

PLACEBO COMPARATOR

Participants received placebo plus Azacitidine.

Drug: Azacitidine; Drug: Placebo

Interventions

Sabatolimab DRUG

A dose of MBG453 800 mg was administered intravenously (IV) every 4 weeks (Q4W).

Also known as: MBG453

Sabatolimab (MBG453) + Azacitidine

Azacitidine DRUG

A dose of Azacitidine 75 mg/m2 was administered IV or subcutaneously (SC) on Day 1-7, or Day 1-5, 8 and 9.

Placebo + Azacitidine; Sabatolimab (MBG453) + Azacitidine

Placebo DRUG

A dose of placebo 800 mg was administered intravenously every 4 weeks (Q4W).

Placebo + Azacitidine

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
• Morphologically confirmed diagnosis of myelodysplastic syndrome (MDS) based on WHO 2016 classification (Arber et al 2016) by local investigator assessment with one of the following Prognostic Risk Categories, based on the revised International Prognostic Scoring System (IPSS-R):
• Very high (\> 6 points)
• High (\> 4.5 - ≤ 6 points)
• Intermediate (\> 3 - ≤ 4.5 points) Or Morphologically confirmed diagnosis of Chronic Myelomonocytic Leukemia -2 based on WHO 2016 classification (Arber et al 2016, including persistent monocytosis) by local investigator assessment with WBC \< 13 x 109/L at time of initial diagnosis
• Indication for azacitidine treatment according to the investigator, based on local standard medical practice and institutional guidelines for treatment decisions
• Not eligible at time of screening for intensive chemotherapy according to the investigator, based on local standard medical practice and institutional guidelines for treatment decisions, including assessment of individual clinical factors such as age, comorbidities and performance status
• Not eligible at 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, including assessment of individual clinical factors such as age, comorbidities, performance status, and donor availability
• 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 checkpoint inhibitors (e.g, anti-CTLA4, anti-PD-1, anti-PD-L1, or anti-PD-L2), cancer vaccines is allowed except if the drug was administered within 4 months prior to randomization
• Previous first-line treatment for intermediate, high, very high risk myelodysplastic syndromes (based on IPSS-R) or CMML with any antineoplastic agents including for example chemotherapy, lenalidomide and hypomethylating agents (HMAs) such as decitibine and azacitidine. However, previous treatment with hydroxyurea or leukopheresis to reduce WBC count is allowed prior to randomization.
• Investigational treatment received within 4 weeks or 5 half-lives of this investigational treatment, whatever is longer, prior to randomization. In case of a checkpoint inhibitor: a minimal interval of 4 months prior to randomization is necessary to allow randomization.
• Subjects with Myelodysplastic syndrome (MDS) based on 2016 WHO classification (Arber et al 2016) with revised International Prognostic Scoring System (IPSS-R) ≤ 3
• Diagnosis of acute myeloid leukemia (AML) including acute promyelocytic leukemia and extra-medullary acute myeloid leukemia, primary or secondary myelofibrosis based on WHO 2016 classification (Arber et al 2016)
• Diagnosis of therapy related myeloid neoplasms based on WHO 2016 classification (Arber et al 2016)
• History of organ or allogeneic hematopoietic stem cell transplant

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (149)

Yuma Regional Cancer Center

Yuma, Arizona, 85364, United States

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University of California LA

Los Angeles, California, 90095, United States

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Yale University School Of Medicine

New Haven, Connecticut, 06520, United States

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Mayo Clinic Jacksonville

Jacksonville, Florida, 32224, United States

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University Of Miami

Miami, Florida, 33136, United States

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Northwestern University

Chicago, Illinois, 60611, United States

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Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

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Hackensack University Medical Ctr

Hackensack, New Jersey, 07601, United States

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Weill Cornell Medicine NY-Presb

New York, New York, 10021, United States

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University of Rochester Medical Ctr

Rochester, New York, 14642, United States

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University of Virginia

Charlottesville, Virginia, 22903, United States

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Novartis Investigative Site

Pilar, Buenos Aires, B1629AHJ, Argentina

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Wooloongabba, Queensland, 4102, Australia

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Clayton, Victoria, 3168, Australia

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Perth, Western Australia, 6000, Australia

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Innsbruck, Tyrol, 6020, Austria

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Graz, 8036, Austria

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Linz, 4020, Austria

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Roeselare, West-Vlaanderen, 8800, Belgium

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Brasschaat, 2930, Belgium

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Florianópolis, Santa Catarina, 88020-210, Brazil

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São Paulo, São Paulo, 04014-002, Brazil

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São Paulo, São Paulo, 05319-000, Brazil

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Calgary, Alberta, T2N 4N2, Canada

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Toronto, Ontario, M4N 3M5, Canada

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Viña del Mar, Región de Valparaíso, 2540364, Chile

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Guangzhou, Guangdong, 510080, China

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Guangzhou, Guangdong, 510515, China

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Shenzhen, Guangdong, 518037, China

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Wuhan, Hubei, 430022, China

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Wuhan, Hubei, 430030, China

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Suzhou, Jiangsu, 215004, China

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Changchun, Jilin, 130021, China

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Chengdu, Sichuan, 610041, China

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Hangzhou, Zhejiang, 310003, China

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Beijing, 100029, China

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Beijing, 100730, China

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Jinan, 250012, China

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Shanghai, 200025, China

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Shanghai, 200233, China

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Tianjin, 300020, China

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Tianjin, 300052, China

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Rionegro, Antioquia, 054047, Colombia

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Bogotá, 110231, Colombia

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Brno, 625 00, Czechia

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Hradec Králové, 500 05, Czechia

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Prague, 128 00, Czechia

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Prague, 128 08, Czechia

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Helsinki, FIN 00290, Finland

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Kuopio, 70211, Finland

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Grenoble, 38043, France

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Lille, 59037, France

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Paris, 75475, France

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Toulouse, 31059, France

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Tours, 37044, France

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Vandœuvre-lès-Nancy, 54511, France

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Frankfurt am Main, Hesse, 60590, Germany

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Velbert, North Rhine-Westphalia, 42551, Germany

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Dresden, Saxony, 01307, Germany

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Jena, Thuringia, 07740, Germany

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Augsburg, 86179, Germany

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Düsseldorf, 40479, Germany

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Greifswald, 17475, Germany

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Kiel, 24116, Germany

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Ulm, 89081, Germany

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Alexandroupoli, 681 00, Greece

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Pátrai, 265 04, Greece

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Ahmedabad, Gujarat, 380009, India

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Faridabad, Haryana, 121 001, India

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Madurai, Tamil Nadu, 625107, India

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Kolkata, West Bengal, 700014, India

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Kolkata, West Bengal, 700160, India

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Delhi, 110085, India

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Afula, 1834111, Israel

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Tel Aviv, 6423906, Israel

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Bologna, BO, 40138, Italy

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Catania, CT, 95123, Italy

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Florence, FI, 50134, Italy

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Genova, GE, 16132, Italy

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Milan, MI, 20162, Italy

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Rozzano, MI, 20089, Italy

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Reggio Calabria, RC, 89124, Italy

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Roma, RM, 00133, Italy

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Nagoya, Aichi-ken, 464 8681, Japan

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Kashiwa, Chiba, 277 8577, Japan

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Fukuoka, Fukuoka, 812-8582, Japan

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Sapporo, Hokkaido, 064 0804, Japan

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Isehara, Kanagawa, 259-1193, Japan

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Sendai, Miyagi, 980 8574, Japan

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Nagasaki, Nagasaki, 852-8501, Japan

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Sakai, Osaka, 590-0197, Japan

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Bunkyo-ku, Tokyo, 113-8603, Japan

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Yamagata, Yamagata, 990 9585, Japan

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Osaka, 545-8586, Japan

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Beirut, 113-0236, Lebanon

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Vilnius, LT-08406, Lithuania

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George Town, Pulau Pinang, 10450, Malaysia

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Kuching, Sarawak, 93586, Malaysia

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Kuala Lumpur, 59100, Malaysia

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Kuala Selangor, 68000, Malaysia

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Satélite, Edo Mexico, 53100, Mexico

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Mexico City, Mexico City, 06720, Mexico

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Morelia, Michoacán, 58260, Mexico

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Estado de México, 52787, Mexico

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Groningen, Provincie Groningen, 9713 GZ, Netherlands

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Khoudh, 123, Oman

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Lisbon, 1099-023, Portugal

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Porto, 4200-072, Portugal

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Saint Petersburg, 191024, Russia

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Saint Petersburg, 197022, Russia

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Riyadh, 11211, Saudi Arabia

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Singapore, 119074, Singapore

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Singapore, 169608, Singapore

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Seoul, Korea, 03080, South Korea

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Seoul, Seoul, 06351, South Korea

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Seoul, 03722, South Korea

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Seoul, 05505, South Korea

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Seoul, 06591, South Korea

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Badalona, Barcelona, 08916, Spain

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Salamanca, Castille and León, 37007, Spain

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Barcelona, Catalonia, 08035, Spain

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Oviedo, Principality of Asturias, 33011, Spain

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Madrid, 28009, Spain

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Seville, 41013, Spain

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Valencia, 46010, Spain

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Valencia, 46026, Spain

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Bern, 3010, Switzerland

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Zurich, 8091, Switzerland

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Hualien City, 970, Taiwan

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Kaohsiung City, 83301, Taiwan

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Liouying Township, 736005, Taiwan

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Taichung, 40447, Taiwan

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Taipei, 10002, Taiwan

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Taoyuan District, 33305, Taiwan

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Songkhla, Hat Yai, 90110, Thailand

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Khon Kaen, THA, 40002, Thailand

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Bangkok, 10330, Thailand

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Bangkok, 10400, Thailand

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Bangkok, 10700, Thailand

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Chiang Mai, 50200, Thailand

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Samsun, Atakum, 55200, Turkey (Türkiye)

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Edirne, Merkez, 22030, Turkey (Türkiye)

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Istanbul, Pendik, 34899, Turkey (Türkiye)

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Ankara, 06230, Turkey (Türkiye)

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Izmir, 35100, Turkey (Türkiye)

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Portsmouth, Hants, PO6 3LY, United Kingdom

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Edinburgh, Scotland, EH4 2XU, United Kingdom

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Manchester, M20 2BX, United Kingdom

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Nottingham, NG5 1PB, United Kingdom

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Related Publications (1)

• Zeidan AM, Giagounidis A, Sekeres MA, Xiao Z, Sanz GF, Hoef MV, Ma F, Hertle S, Santini V. STIMULUS-MDS2 design and rationale: a phase III trial with the anti-TIM-3 sabatolimab (MBG453) + azacitidine in higher risk MDS and CMML-2. Future Oncol. 2023 Mar;19(9):631-642. doi: 10.2217/fon-2022-1237. Epub 2023 Apr 21.

  PMID: 37083373 DERIVED

Related Links

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

MeSH Terms

Conditions

Myelodysplastic Syndromes; Leukemia, Myelomonocytic, Chronic

Interventions

sabatolimab; Azacitidine

Condition Hierarchy (Ancestors)

Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases; Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Myelodysplastic-Myeloproliferative Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Aza Compounds; Organic Chemicals; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides

Limitations and Caveats

A total of 530 participants were randomized (265 to sabatolimab+AZA, 265 to placebo+AZA), but 1 participant in each arm did not receive any study treatment and were excluded from the Safety Set. Another sabatolimab-assigned participant received only AZA and thus was summarized in the placebo+AZA arm in all safety analyses. Therefore, the Serious and Other Adverse Events were shown for 263 sabatolimab+AZA and 265 placebo+AZA participants.

Results Point of Contact

• Title: Study Director
• Organization: Novartis Pharmaceuticals

novartis.email@novartis.com

862-778-3000

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 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Randomized, double-blind

Study Record Dates

• First Submitted: January 21, 2020
• First Posted: February 12, 2020
• Study Start: June 8, 2020
• Primary Completion: October 2, 2024
• Study Completion: October 2, 2024
• Last Updated: January 13, 2026
• Results First Posted: December 12, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will share

Locations

CZ (4); TU (5); LE (1); ME (4); OM (1); IT (8); LI (1); TH (6); GR (2); DE (9); AR (1); IN (6); AU (3); CA (2); JP (11); NL (1); GB (4); TW (6); BE (2); CL (1); CO (2); FR (6); KR (5); FI (2); IL (2); PT (2); BR (3); MY (4); CN (16); US (11); SG (2); ES (8); SA (1); RU (2); CH (2)