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) (STIMULUS-MDS2)

A Randomized, Double-blind, Placebo-controlled Phase III Multi-center Study of Azacitidine With or Without MBG453 for the Treatment of Patients With Intermediate, High or Very High Risk Myelodysplastic Syndrome (MDS) as Per IPSS-R, or Chronic Myelomonocytic Leukemia-2 (CMML-2)

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.

Study Overview

• Status: Terminated
• Conditions: Myelodysplastic Syndromes; Leukemia, Myelomonocytic, Chronic
• Intervention / Treatment: Drug: Sabatolimab; Drug: Azacitidine; Drug: Placebo

Detailed Description

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).

The primary objective of this study was to compare overall survival (OS) in the MBG453 plus azacitidine arm versus placebo plus azacitidine arm where OS was the time from randomization until death due to any cause.

Participants were randomized in a 1:1 ratio to treatment arms as follow: MBG453 800 mg IV Q4W plus azacitidine, Placebo IV Q4W plus azacitidine.

The randomization was stratified into 4 groups: intermediate risk MDS, high risk MDS, very high risk MDS and CMML-2.

All participants who discontinued both study treatments were to have entered a long-term post-treatment follow-up including response and PRO assessments, and/or survival follow-up for up to 5 years after the last participant was randomized.

Participants were receiving treatment until they experienced progression of disease (including transformation to acute leukemia per WHO 2016 classification), experienced unacceptable toxicity or discontinued the study treatment for other reasons.

Continuation of study treatment beyond progression (excluding transformation to acute leukemia: continuation in this case was not possible) could have been possible in selected participants.

• Study Type: Interventional
• Enrollment (Actual): 530
• Phase: Phase 3

Contacts and Locations

Study Locations

• Argentina
  • Buenos Aires
    • Pilar, Buenos Aires, Argentina, B1629AHJ
      • Novartis Investigative Site
• Australia
  • Queensland
    • Wooloongabba, Queensland, Australia, 4102
      • Novartis Investigative Site
  • Victoria
    • Clayton, Victoria, Australia, 3168
      • Novartis Investigative Site
  • Western Australia
    • Perth, Western Australia, Australia, 6000
      • Novartis Investigative Site
• Austria
  • Graz, Austria, 8036
    • Novartis Investigative Site
  • Linz, Austria, 4020
    • Novartis Investigative Site
  • Tyrol
    • Innsbruck, Tyrol, Austria, 6020
      • Novartis Investigative Site
• Belgium
  • Brasschaat, Belgium, 2930
    • Novartis Investigative Site
  • West-Vlaanderen
    • Roeselare, West-Vlaanderen, Belgium, 8800
      • Novartis Investigative Site
• Brazil
  • Santa Catarina
    • Florianópolis, Santa Catarina, Brazil, 88020-210
      • Novartis Investigative Site
  • São Paulo
    • São Paulo, São Paulo, Brazil, 04014-002
      • Novartis Investigative Site
    • São Paulo, São Paulo, Brazil, 05319-000
      • Novartis Investigative Site
• Canada
  • Alberta
    • Calgary, Alberta, Canada, T2N 4N2
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  • Ontario
    • Toronto, Ontario, Canada, M4N 3M5
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• Chile
  • Región de Valparaíso
    • Viña del Mar, Región de Valparaíso, Chile, 2540364
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• China
  • Beijing, China, 100730
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  • Beijing, China, 100029
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  • Jinan, China, 250012
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  • Shanghai, China, 200025
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  • Shanghai, China, 200233
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  • Tianjin, China, 300052
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  • Tianjin, China, 300020
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  • Guangdong
    • Guangzhou, Guangdong, China, 510080
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    • Guangzhou, Guangdong, China, 510515
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    • Shenzhen, Guangdong, China, 518037
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  • Hubei
    • Wuhan, Hubei, China, 430030
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    • Wuhan, Hubei, China, 430022
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  • Jiangsu
    • Suzhou, Jiangsu, China, 215004
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  • Jilin
    • Changchun, Jilin, China, 130021
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  • Sichuan
    • Chengdu, Sichuan, China, 610041
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  • Zhejiang
    • Hangzhou, Zhejiang, China, 310003
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• Colombia
  • Bogotá, Colombia, 110231
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  • Antioquia
    • Rionegro, Antioquia, Colombia, 054047
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• Czechia
  • Brno, Czechia, 625 00
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  • Hradec Králové, Czechia, 500 05
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  • Prague, Czechia, 128 08
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  • Prague, Czechia, 128 00
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• Finland
  • Helsinki, Finland, FIN 00290
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  • Kuopio, Finland, 70211
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• France
  • Grenoble, France, 38043
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  • Lille, France, 59037
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  • Paris, France, 75475
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  • Toulouse, France, 31059
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  • Tours, France, 37044
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  • Vandœuvre-lès-Nancy, France, 54511
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• Germany
  • Augsburg, Germany, 86179
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  • Düsseldorf, Germany, 40479
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  • Greifswald, Germany, 17475
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  • Kiel, Germany, 24116
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  • Ulm, Germany, 89081
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  • Hesse
    • Frankfurt am Main, Hesse, Germany, 60590
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  • North Rhine-Westphalia
    • Velbert, North Rhine-Westphalia, Germany, 42551
      • Novartis Investigative Site
  • Saxony
    • Dresden, Saxony, Germany, 01307
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  • Thuringia
    • Jena, Thuringia, Germany, 07740
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• Greece
  • Alexandroupoli, Greece, 681 00
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  • Pátrai, Greece, 265 04
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• India
  • Delhi, India, 110085
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  • Gujarat
    • Ahmedabad, Gujarat, India, 380009
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  • Haryana
    • Faridabad, Haryana, India, 121 001
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  • Tamil Nadu
    • Madurai, Tamil Nadu, India, 625107
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  • West Bengal
    • Kolkata, West Bengal, India, 700160
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    • Kolkata, West Bengal, India, 700014
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• Israel
  • Afula, Israel, 1834111
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  • Tel Aviv, Israel, 6423906
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• Italy
  • BO
    • Bologna, BO, Italy, 40138
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  • CT
    • Catania, CT, Italy, 95123
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  • FI
    • Florence, FI, Italy, 50134
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  • GE
    • Genova, GE, Italy, 16132
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  • MI
    • Milan, MI, Italy, 20162
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    • Rozzano, MI, Italy, 20089
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  • RC
    • Reggio Calabria, RC, Italy, 89124
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  • RM
    • Roma, RM, Italy, 00133
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• Japan
  • Osaka, Japan, 545-8586
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  • Aichi-ken
    • Nagoya, Aichi-ken, Japan, 464 8681
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  • Chiba
    • Kashiwa, Chiba, Japan, 277 8577
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  • Fukuoka
    • Fukuoka, Fukuoka, Japan, 812-8582
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  • Hokkaido
    • Sapporo, Hokkaido, Japan, 064 0804
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  • Kanagawa
    • Isehara, Kanagawa, Japan, 259-1193
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  • Miyagi
    • Sendai, Miyagi, Japan, 980 8574
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  • Nagasaki
    • Nagasaki, Nagasaki, Japan, 852-8501
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  • Osaka
    • Sakai, Osaka, Japan, 590-0197
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  • Tokyo
    • Bunkyo-ku, Tokyo, Japan, 113-8603
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  • Yamagata
    • Yamagata, Yamagata, Japan, 990 9585
      • Novartis Investigative Site
• Lebanon
  • Beirut, Lebanon, 113-0236
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• Lithuania
  • Vilnius, Lithuania, LT-08406
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• Malaysia
  • Kuala Lumpur, Malaysia, 59100
    • Novartis Investigative Site
  • Kuala Selangor, Malaysia, 68000
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  • Pulau Pinang
    • George Town, Pulau Pinang, Malaysia, 10450
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  • Sarawak
    • Kuching, Sarawak, Malaysia, 93586
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• Mexico
  • Estado de México, Mexico, 52787
    • Novartis Investigative Site
  • Edo Mexico
    • Satélite, Edo Mexico, Mexico, 53100
      • Novartis Investigative Site
  • Mexico City
    • Mexico City, Mexico City, Mexico, 06720
      • Novartis Investigative Site
  • Michoacán
    • Morelia, Michoacán, Mexico, 58260
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• Netherlands
  • Provincie Groningen
    • Groningen, Provincie Groningen, Netherlands, 9713 GZ
      • Novartis Investigative Site
• Oman
  • Khoudh, Oman, 123
    • Novartis Investigative Site
• Portugal
  • Lisbon, Portugal, 1099-023
    • Novartis Investigative Site
  • Porto, Portugal, 4200-072
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• Russia
  • Saint Petersburg, Russia, 197022
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  • Saint Petersburg, Russia, 191024
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• Saudi Arabia
  • Riyadh, Saudi Arabia, 11211
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• Singapore
  • Singapore, Singapore, 119074
    • Novartis Investigative Site
  • Singapore, Singapore, 169608
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• South Korea
  • Seoul, South Korea, 05505
    • Novartis Investigative Site
  • Seoul, South Korea, 03722
    • Novartis Investigative Site
  • Seoul, South Korea, 06591
    • Novartis Investigative Site
  • Korea
    • Seoul, Korea, South Korea, 03080
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  • Seoul
    • Seoul, Seoul, South Korea, 06351
      • Novartis Investigative Site
• Spain
  • Madrid, Spain, 28009
    • Novartis Investigative Site
  • Seville, Spain, 41013
    • Novartis Investigative Site
  • Valencia, Spain, 46026
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  • Valencia, Spain, 46010
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  • Barcelona
    • Badalona, Barcelona, Spain, 08916
      • Novartis Investigative Site
  • Castille and León
    • Salamanca, Castille and León, Spain, 37007
      • Novartis Investigative Site
  • Catalonia
    • Barcelona, Catalonia, Spain, 08035
      • Novartis Investigative Site
  • Principality of Asturias
    • Oviedo, Principality of Asturias, Spain, 33011
      • Novartis Investigative Site
• Switzerland
  • Bern, Switzerland, 3010
    • Novartis Investigative Site
  • Zurich, Switzerland, 8091
    • Novartis Investigative Site
• Taiwan
  • Hualien City, Taiwan, 970
    • Novartis Investigative Site
  • Kaohsiung City, Taiwan, 83301
    • Novartis Investigative Site
  • Liouying Township, Taiwan, 736005
    • Novartis Investigative Site
  • Taichung, Taiwan, 40447
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  • Taipei, Taiwan, 10002
    • Novartis Investigative Site
  • Taoyuan District, Taiwan, 33305
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• Thailand
  • Bangkok, Thailand, 10330
    • Novartis Investigative Site
  • Bangkok, Thailand, 10700
    • Novartis Investigative Site
  • Bangkok, Thailand, 10400
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  • Chiang Mai, Thailand, 50200
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  • Hat Yai
    • Songkhla, Hat Yai, Thailand, 90110
      • Novartis Investigative Site
  • THA
    • Khon Kaen, THA, Thailand, 40002
      • Novartis Investigative Site
• Turkey (Türkiye)
  • Ankara, Turkey (Türkiye), 06230
    • Novartis Investigative Site
  • Izmir, Turkey (Türkiye), 35100
    • Novartis Investigative Site
  • Atakum
    • Samsun, Atakum, Turkey (Türkiye), 55200
      • Novartis Investigative Site
  • Merkez
    • Edirne, Merkez, Turkey (Türkiye), 22030
      • Novartis Investigative Site
  • Pendik
    • Istanbul, Pendik, Turkey (Türkiye), 34899
      • Novartis Investigative Site
• United Kingdom
  • Manchester, United Kingdom, M20 2BX
    • Novartis Investigative Site
  • Nottingham, United Kingdom, NG5 1PB
    • Novartis Investigative Site
  • Hants
    • Portsmouth, Hants, United Kingdom, PO6 3LY
      • Novartis Investigative Site
  • Scotland
    • Edinburgh, Scotland, United Kingdom, EH4 2XU
      • Novartis Investigative Site
• United States
  • Arizona
    • Yuma, Arizona, United States, 85364
      • Yuma Regional Cancer Center
  • California
    • Los Angeles, California, United States, 90095
      • University of California LA
  • Connecticut
    • New Haven, Connecticut, United States, 06520
      • Yale University School of Medicine
  • Florida
    • Jacksonville, Florida, United States, 32224
      • Mayo Clinic Jacksonville
    • Miami, Florida, United States, 33136
      • University of Miami
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Northwestern University
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital
  • New Jersey
    • Hackensack, New Jersey, United States, 07601
      • Hackensack University Medical Ctr
  • New York
    • New York, New York, United States, 10021
      • Weill Cornell Medicine NY-Presb
    • Rochester, New York, United States, 14642
      • University of Rochester Medical Ctr
  • Virginia
    • Charlottesville, Virginia, United States, 22903
      • University of Virginia

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

• 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

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 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Sabatolimab (MBG453) + Azacitidine; Participants received sabatolimab plus Azacitidine	Drug: Sabatolimab; A dose of MBG453 800 mg was administered intravenously (IV) every 4 weeks (Q4W).; Other Names: MBG453; Drug: Azacitidine; 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 Comparator: Placebo + Azacitidine; Participants received placebo plus Azacitidine.	Drug: Azacitidine; A dose of Azacitidine 75 mg/m2 was administered IV or subcutaneously (SC) on Day 1-7, or Day 1-5, 8 and 9.; Drug: Placebo; A dose of placebo 800 mg was administered intravenously every 4 weeks (Q4W).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Key Secondary Endpoint 1: Time to Definitive Deterioration of Fatigue Using Functional Assessment of Cancer Therapy (FACIT)-Fatigue Score	FACIT-Fatigue score is a 13-item questionnaire designed to assess fatigue in cancer participants. All items use a 5-point scale ranging from 0 to 4 (0=Not at All to 4=Very Much). The total score ranges from 0 to 52 with higher values representing better quality of life. Time to definitive deterioration of fatigue is defined as time from randomization to at least 3 points worsening from baseline in FACIT-fatigue scores with no subsequently observed improvement above this threshold, or death due to any cause, whichever occurred first.	up to approx. 52 months
Key Secondary Endpoint 2: Red Blood Cell (RBC) Annualized Transfusion Free Rate for Transfusion	Annualized transfusion free rate is defined as the average number of days in RBC transfusion-free intervals in a year (i.e., the total number of days in RBC transfusion-free intervals divided by the total days in the study multiplied by 365.25), where RBC transfusion-free intervals correspond to cumulative times of intervals with no evidence of RBC transfusion for at least 8 weeks at any point after randomization until death due to any cause.	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	FACIT-Fatigue score is a 13-item questionnaire designed to assess fatigue in cancer participants. All items use a 5-point scale ranging from 0 to 4 (0=Not at All to 4=Very Much). The total score ranges from 0 to 52 with higher values representing better quality of life. The responder is defined as having 3 points improvement from baseline confirmed by a second improvement of 3 points at any time, regardless of preceding worsening. A participant who could not improve was considered as a non-responder.	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)	EORTC-QLQ-C30 is a 30-item questionnaire developed to assess the quality of life of cancer participants. Participants' responses to 5 questions about their physical functioning (Items 1-5) are scored on a 4-point scale (1=Not at All to 4=Very Much). Using linear transformation, raw scores are standardized, so that scores range from 0 to 100. A high score indicates a high / healthy level of functioning. The responder is defined as having 10 points improvement from baseline confirmed by a second improvement of 10 points at any time, regardless of preceding worsening. A participant who could not improve was considered as a non-responder.	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	EORTC-QLQ-C30 is a 30-item questionnaire developed to assess the quality of life of cancer participants. Participants' responses to 4 questions about their emotional functioning (Items 21-24) are scored on a 4-point scale (1=Not at All to 4=Very Much). Using linear transformation, raw scores are standardized, so that scores range from 0 to 100. A high score indicates a high / healthy level of functioning. The responder is defined as having 10 points improvement from baseline confirmed by a second improvement of 10 points at any time, regardless of preceding worsening. A participant who could not improve was considered as a non-responder.	up to approx. 52 months
Percentage of Participants With Either CR, or mCR, or PR, or HI in Each Treatment Arm According to International Working Group for MDS (IWG-MDS) as Per Investigator Assessment	Response rate of participants with complete remission (CR), or marrow remission (mCR), or partial remission (PR), or hematologic improvement (HI). 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%. mCR: Bone marrow: ≤ 5% blasts and blast count decrease by ≥ 50% compared to baseline; Peripheralblood/transfusion: Marrow CR may be achieved with or without improved blood counts or with or without transfusions PR: All CR criteria except bone marrow: ≥50% decrease from baseline in blasts in bone marrow AND blast count in bone marrow >5%. HI: restoration or enhancement of the function of the body's blood cell-producing system that must last as least 8 weeks.	up to approx. 52 months
Percentage of Participants With Stable Disease (SD) According to International Working Group for MDS (IWG-MDS) as Per Investigator Assessment	Response rate of participants with stable disease. SD is the failure to achieve at least partial response (PR), but no evidence of progression for >8 weeks.	up to approx. 52 months
Progression Free Survival (PFS)	PFS is defined as the time from randomization to disease progression (including transformation to acute leukemia per WHO 2016), relapse from CR (IWG-MDS), or death. Disease progression: bone marrow blasts increase ≥ 50% over baseline, to > 5% if initially < 5%, > 10% if 5%-<10%, or > 20% if 10%-<20%. Includes a peripheral blood count decrease ≥ 50% from maximum remission/response levels: neutrophils < 1.0x109/L, platelets < 100x109/L, or hemoglobin drop ≥ 2 g/dL to < 10 g/dL, becoming transfusion-dependent. Relapse from CR: baseline bone marrow blast % return, neutrophils decrease ≥ 50% to < 1.0x109/L, platelets decrease ≥ 50% to < 100x109/L, or hemoglobin drop ≥ 1.5 g/dL to < 10 g/dL, becoming transfusion-dependent. Leukemia transformation: > 20% blasts per WHO 2016 (Arber et al 2016).	up to approx. 52 months
Leukemia-free Survival (LFS)	LFS is defined as the time from randomization to ≥ 20% blasts in bone marrow/peripheral blood (per WHO 2016 classification) or diagnosis of extramedullary acute leukemia, or death due to any cause	up to approx. 52 months
Number of Participants Who Become Red Blood Cells (RBC) Transfusion Independent After Randomization	Improvement in RBC transfusion independence as per International Working Group for MDS (IWG-MDS) criteria. RBC transfusion independence was defined as having received 0 units of RBC transfusions during at least 8 consecutive weeks after randomization. The number of participants was shown in only those with transfusion dependence at baseline (BL).	up to approx. 52 months
Number of Participants Who Become Platelets Transfusion Independent After Randomization	Improvement in Platelets transfusion independence as per International Working Group for MDS (IWG-MDS) criteria. Platelets transfusion independence was defined as having received 0 units of Platelets transfusions during at least 8 consecutive weeks after randomization. The number of participants was shown in only those with transfusion dependence at baseline (BL).	up to approx. 52 months
Pharmacokinetics of MBG453 (Parameter Cmax)	Cmax is the maximum (peak) observed drug concentration after single dose administration (mass x volume-1).	0 hr (pre-dose) & 2 hrs (post-dose) of Cycle (C) 1 Day (D) 8 and 0 hr (pre-dose) & 2 hrs (post-dose) of C3D8
Pharmacokinetics of MBG453 (Parameter AUC)	AUCinf is the AUC from time zero to infinity (mass x time x volume-1).	0 hr (pre-dose) & 2 hrs (post-dose) of Cycle (C) 1 Day (D) 8 and 0 hr (pre-dose) & 2 hrs (post-dose) of C3D8
ADA Prevalence at Baseline and ADA-positive Participants On-treatment	Anti-drug Antibody (ADA) prevalence is the number of participants with at least one sample meeting the criteria at baseline. ADA-positive participants were calculated as the number of participants with at least one on-treatment ADA-positive sample divided by the number of participants with a determinant baseline IG sample and at least one determinant post-baseline IG sample.	Baseline, up to approx. 39 months
Change From Baseline in the European Quality of Life (EuroQol) - 5 Dimensions, 5 Level Questionnaire (EQ-5D-5L) Score Over Time	The EQ-5D-5L comprises 5 dimensions: mobility, self-care, usual activities, pain/discomfort, anxiety/depression. For each of the 5 dimensions, subject's responses are scored on a 5-point scale (1=no problem to 5=extreme problems). Change from baseline is being presented for EQ Index score. Index score is defined as a weighted combination of the levels of the 5-dimention scales, ranging from 0 to 1 (perfect health), with higher scores indicating better health-related quality of life. The United States value set from Pickard et al 2019 was used.	Baseline, every 3 cycles up to C48D1 (1 cycle = 28 days)
Change From Baseline in the European Quality of Life (EuroQoL) - 5 Dimensions, 5 Level Questionnaire (EQ-5D-5L) Visual Analogue Scale (VAS) Over Time	The EQ-5D-5L VAS records the participant's self-rated health on a visual analogue scale numbered from 0 to 100, with 0 being "the worst health you can imagine" and 100 being "the best health you can imagine". Change from baseline was presented.	Baseline, every 3 cycles up to C48D1 (1 cycle = 28 days)
Change From Baseline of Global Health Status/Quality of Life Scores Using European Organization for Research and Treatment of Cancer's Core Quality of Life Questionnaire (EORTC-QLQ-C30).	EORTC-QLQ-C30 is a 30-item questionnaire developed to assess the quality of life of cancer participants. Participant's responses to 2 questions (Items 29+30: "How would you rate your overall health during the past week?" and "How would you rate your overall quality of life during the past week?") are scored on a 7-point scale (1=Very Poor to 7=Excellent). Using linear transformation, raw scores are standardized, so that scores range from 0 to 100. A higher score indicates a better overall outcome. Change from baseline to Cycle 12 Day 1 as presented.	Up to Cycle 12 Day 1 (C12D1) (1 cycle = 28 days)

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals
• Investigators: Study Director: Novartis Pharmaceuticals, Novartis Pharmaceuticals

Publications and helpful links

General Publications

• 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.

Helpful Links

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

Study record dates

Study Major Dates

• Study Start (Actual): June 8, 2020
• Primary Completion (Actual): October 2, 2024
• Study Completion (Actual): October 2, 2024

Study Registration Dates

• First Submitted: January 21, 2020
• First Submitted That Met QC Criteria: February 10, 2020
• First Posted (Actual): February 12, 2020

Study Record Updates

• Last Update Posted (Estimated): January 13, 2026
• Last Update Submitted That Met QC Criteria: December 18, 2025
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Keywords: Phase III; chronic myelomonocytic leukemia; MDS; TIM-3; MBG453; myelodysplastic syndrome; azacitidine; CMML-2; Sabatolimab; high or; very high risk myelodysplastic syndrome; Chronic Myelomonocytic Leukemia-2
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms; Chronic Disease; Disease Attributes; Neoplasms by Histologic Type; Hematologic Diseases; Leukemia, Myeloid; Myelodysplastic-Myeloproliferative Diseases; Bone Marrow Diseases; Leukemia; Pathological Conditions, Signs and Symptoms; Hemic and Lymphatic Diseases; Leukemia, Myelomonocytic, Chronic; Myelodysplastic Syndromes; Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleic Acids, Nucleotides, and Nucleosides; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Aza Compounds; Nucleosides; Ribonucleosides; Azacitidine; sabatolimab
• Other Study ID Numbers: CMBG453B12301; 2019-002089-11 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

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 participants 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

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No