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 is a Phase III multi-center, randomized, two-arm parallel-group, double-blind, placebo-controlled study of MBG453 or placebo added to azacitidine in adult subjects 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 is to assess clinical effects of MBG453 in combination with azacitidine in adult subjects with IPSS-R intermediate, high, very high risk MDS and CMML-2.

Study Overview

• Status: Active, not recruiting
• Conditions: Myelodysplastic Syndromes; Leukemia, Myelomonocytic, Chronic
• Intervention / Treatment: Drug: Azacitidine; Drug: Placebo; Drug: Sabatolimab

Detailed Description

This is a Phase III multi-center, randomized, two-arm parallel-group, double-blind, placebo controlled study of MBG453 or placebo added to azacitidine in adult subjects 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 is to compare overall survival (OS) in the MBG453 plus azacitidine arm versus placebo plus azacitidine arm where OS is the time from randomization until death due to any cause.

Subjects will be randomized in a 1:1 ratio to treatment arms as follow: MBG453 800 mg IV Q4W plus azacytidine, Placebo IV Q4W plus azacitidine The randomization will be stratified into 4 groups: intermediate risk MDS, high risk MDS, very high risk MDS and CMML-2.

All subjects who discontinue both study treatments will enter 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 subject was randomized.

Subjects will be treated until they experience progression of disease (including transformation to acute leukemia per WHO 2016 classification), experience unacceptable toxicity or discontinue the study treatment for other reasons.

Continuation of study treatment beyond progression (excluding transformation to acute leukemia: continuation in this case is not possible) may be possible in selected subjects.

• 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
    • Woolloongabba, 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
  • Innsbruck, Austria, A-6020
    • Novartis Investigative Site
  • Linz, Austria, A-4010
    • Novartis Investigative Site
• Belgium
  • Brasschaat, Belgium, 2930
    • Novartis Investigative Site
  • Roeselare, Belgium, 8800
    • Novartis Investigative Site
• Brazil
  • SC
    • Florianopolis, SC, Brazil, 88034-000
      • Novartis Investigative Site
  • SP
    • Sao Paulo, SP, Brazil, 04014-002
      • Novartis Investigative Site
    • Sao Paulo, SP, Brazil, 05319-000
      • Novartis Investigative Site
• Canada
  • Alberta
    • Calgary, Alberta, Canada, T2N 4N2
      • Novartis Investigative Site
  • Ontario
    • Toronto, Ontario, Canada, M4N 3M5
      • Novartis Investigative Site
• Chile
  • Valparaiso
    • Vina del Mar, Valparaiso, Chile, 2540364
      • Novartis Investigative Site
• China
  • Beijing, China, 100730
    • Novartis Investigative Site
  • Beijing, China, 100029
    • Novartis Investigative Site
  • Chengdu, China, 610041
    • Novartis Investigative Site
  • Jinan, China, 250012
    • Novartis Investigative Site
  • Shanghai, China, 200025
    • Novartis Investigative Site
  • Shanghai, China, 200233
    • Novartis Investigative Site
  • Tianjin, China, 300052
    • Novartis Investigative Site
  • Tianjin, China, 300020
    • Novartis Investigative Site
  • Guangdong
    • Guangzhou, Guangdong, China, 51000
      • Novartis Investigative Site
    • Guangzhou, Guangdong, China, 510515
      • Novartis Investigative Site
    • Shenzhen, Guangdong, China, 518037
      • Novartis Investigative Site
  • Hubei
    • Wuhan, Hubei, China, 430030
      • Novartis Investigative Site
    • Wuhan, Hubei, China, 430022
      • Novartis Investigative Site
  • Jiangsu
    • Suzhou, Jiangsu, China, 215006
      • Novartis Investigative Site
  • Jilin
    • Chang Chun, Jilin, China, 130021
      • Novartis Investigative Site
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310003
      • Novartis Investigative Site
• Colombia
  • Bogota, Colombia, 110231
    • Novartis Investigative Site
  • Antioquia
    • Rionegro, Antioquia, Colombia, 054047
      • Novartis Investigative Site
• Czechia
  • Brno - Bohunice, Czechia, 625 00
    • Novartis Investigative Site
  • Praha, Czechia, 12808
    • Novartis Investigative Site
  • CZE
    • Hradec Kralove, CZE, Czechia, 500 05
      • Novartis Investigative Site
  • Czech Republic
    • Praha 2, Czech Republic, Czechia, 128 20
      • Novartis Investigative Site
• Finland
  • Helsinki, Finland, FIN 00290
    • Novartis Investigative Site
  • Kuopio, Finland, 70211
    • Novartis Investigative Site
• France
  • Grenoble, France, 38043
    • Novartis Investigative Site
  • Lille, France, 59037
    • Novartis Investigative Site
  • Paris 10, France, 75475
    • Novartis Investigative Site
  • Toulouse, France, 31059
    • Novartis Investigative Site
  • Tours, France, 37044
    • Novartis Investigative Site
  • Vandoeuvre Les Nancy, France, 54511
    • Novartis Investigative Site
• Germany
  • Augsburg, Germany, 86179
    • Novartis Investigative Site
  • Duesseldorf, Germany, 40479
    • Novartis Investigative Site
  • Frankfurt, Germany, 60590
    • Novartis Investigative Site
  • Greifswald, Germany, 17475
    • Novartis Investigative Site
  • Jena, Germany, 07740
    • Novartis Investigative Site
  • Kiel, Germany, 24116
    • Novartis Investigative Site
  • Ulm, Germany, 89081
    • Novartis Investigative Site
  • North Rhine-Westphalia
    • Velbert, North Rhine-Westphalia, Germany, 42551
      • Novartis Investigative Site
  • Sachsen
    • Dresden, Sachsen, Germany, 01307
      • Novartis Investigative Site
• Greece
  • Patras, Greece, 265 00
    • Novartis Investigative Site
  • Evros
    • Alexandroupolis, Evros, Greece, 681 00
      • Novartis Investigative Site
• India
  • Delhi, India, 110 085
    • Novartis Investigative Site
  • Gujrat
    • Ahmedabad, Gujrat, India, 380009
      • Novartis Investigative Site
  • Haryana
    • Faridabad, Haryana, India, 121 001
      • Novartis Investigative Site
  • Tamil NADU
    • Madurai, Tamil NADU, India, 625107
      • Novartis Investigative Site
  • West Bengal
    • Kolkata, West Bengal, India, 700160
      • Novartis Investigative Site
    • Kolkata, West Bengal, India, 700014
      • Novartis Investigative Site
• Israel
  • Afula, Israel, 1834111
    • Novartis Investigative Site
  • Tel Aviv, Israel, 6423906
    • Novartis Investigative Site
• Italy
  • BO
    • Bologna, BO, Italy, 40138
      • Novartis Investigative Site
  • CT
    • Catania, CT, Italy, 95123
      • Novartis Investigative Site
  • FI
    • Firenze, FI, Italy, 50134
      • Novartis Investigative Site
  • GE
    • Genova, GE, Italy, 16132
      • Novartis Investigative Site
  • MI
    • Milano, MI, Italy, 20162
      • Novartis Investigative Site
    • Rozzano, MI, Italy, 20089
      • Novartis Investigative Site
  • RC
    • Reggio Calabria, RC, Italy, 89124
      • Novartis Investigative Site
  • RM
    • Roma, RM, Italy, 00133
      • Novartis Investigative Site
• Japan
  • Osaka, Japan, 545-8586
    • Novartis Investigative Site
  • Yamagata, Japan, 990 9585
    • Novartis Investigative Site
  • Aichi
    • Nagoya, Aichi, Japan, 464 8681
      • Novartis Investigative Site
  • Chiba
    • Kashiwa, Chiba, Japan, 277 8577
      • Novartis Investigative Site
  • Fukuoka
    • Fukuoka city, Fukuoka, Japan, 812-8582
      • Novartis Investigative Site
  • Hokkaido
    • Sapporo, Hokkaido, Japan, 064 0804
      • Novartis Investigative Site
  • Kanagawa
    • Isehara, Kanagawa, Japan, 259-1193
      • Novartis Investigative Site
  • Miyagi
    • Sendai city, Miyagi, Japan, 980 8574
      • Novartis Investigative Site
  • Nagasaki
    • Nagasaki-city, Nagasaki, Japan, 852-8501
      • Novartis Investigative Site
  • Osaka
    • Osaka Sayama, Osaka, Japan, 589 8511
      • Novartis Investigative Site
  • Tokyo
    • Bunkyo-ku, Tokyo, Japan, 113-8603
      • Novartis Investigative Site
• Korea, Republic of
  • Seoul, Korea, Republic of, 03080
    • Novartis Investigative Site
  • Seoul, Korea, Republic of, 06351
    • Novartis Investigative Site
  • Seoul, Korea, Republic of, 03722
    • Novartis Investigative Site
  • Seoul, Korea, Republic of, 05505
    • Novartis Investigative Site
  • Seocho Gu
    • Seoul, Seocho Gu, Korea, Republic of, 06591
      • Novartis Investigative Site
• Lebanon
  • Beirut, Lebanon, 1107 2020
    • Novartis Investigative Site
• Lithuania
  • Vilnius, Lithuania, LT-08661
    • Novartis Investigative Site
• Malaysia
  • Kuala Lumpur, Malaysia, 59100
    • Novartis Investigative Site
  • Pulau Pinang, Malaysia, 10990
    • Novartis Investigative Site
  • Selangor, Malaysia, 68000
    • Novartis Investigative Site
  • Sarawak
    • Kuching, Sarawak, Malaysia, 93586
      • Novartis Investigative Site
• Mexico
  • Estado de Mexico, Mexico, 52787
    • Novartis Investigative Site
  • Distrito Federal
    • Mexico, Distrito Federal, Mexico, 06726
      • Novartis Investigative Site
  • Edo Mexico
    • Satelite, Edo Mexico, Mexico, 53100
      • Novartis Investigative Site
  • Michoacan
    • Morelia, Michoacan, Mexico, 58260
      • Novartis Investigative Site
• Netherlands
  • Groningen, Netherlands, 9713 GZ
    • Novartis Investigative Site
• Oman
  • Muscat, Oman, 123
    • Novartis Investigative Site
• Portugal
  • Lisboa, Portugal, 1099 023
    • Novartis Investigative Site
  • Porto, Portugal, 4200-072
    • Novartis Investigative Site
• Russian Federation
  • Saint Petersburg, Russian Federation, 197022
    • Novartis Investigative Site
  • St Petersburg, Russian Federation, 191024
    • Novartis Investigative Site
• Saudi Arabia
  • Riyadh, Saudi Arabia, 11211
    • Novartis Investigative Site
• Singapore
  • Singapore, Singapore, 119228
    • Novartis Investigative Site
  • Singapore, Singapore, 169608
    • Novartis Investigative Site
• Spain
  • Madrid, Spain, 28009
    • Novartis Investigative Site
  • Valencia, Spain, 46026
    • Novartis Investigative Site
  • Andalucia
    • Sevilla, Andalucia, Spain, 41013
      • Novartis Investigative Site
  • Asturias
    • Oviedo, Asturias, Spain, 33011
      • Novartis Investigative Site
  • Castilla Y Leon
    • Salamanca, Castilla Y Leon, Spain, 37007
      • Novartis Investigative Site
  • Catalunya
    • Badalona, Catalunya, Spain, 08916
      • Novartis Investigative Site
    • Barcelona, Catalunya, Spain, 08035
      • Novartis Investigative Site
  • Comunidad Valenciana
    • Valencia, Comunidad Valenciana, Spain, 46010
      • Novartis Investigative Site
• Switzerland
  • Bern, Switzerland, 3010
    • Novartis Investigative Site
  • Zürich, Switzerland, 8091
    • Novartis Investigative Site
• Taiwan
  • Kaohsiung, Taiwan, 83301
    • Novartis Investigative Site
  • Liouying Township, Taiwan, 736005
    • Novartis Investigative Site
  • Taichung, Taiwan, 40447
    • Novartis Investigative Site
  • Taipei, Taiwan, 10002
    • Novartis Investigative Site
  • Taoyuan, Taiwan, 33305
    • Novartis Investigative Site
  • Hualien
    • Hualien City, Hualien, Taiwan, 970
      • Novartis Investigative Site
• Thailand
  • Bangkok, Thailand, 10330
    • Novartis Investigative Site
  • Bangkok, Thailand, 10700
    • Novartis Investigative Site
  • Bangkok, Thailand, 10400
    • Novartis Investigative Site
  • Chiang Mai, Thailand, 50200
    • Novartis Investigative Site
  • Hat Yai
    • Songkhla, Hat Yai, Thailand, 90110
      • Novartis Investigative Site
  • THA
    • Khon Kaen, THA, Thailand, 40002
      • Novartis Investigative Site
• Turkey
  • Ankara, Turkey, 06100
    • Novartis Investigative Site
  • Edirne, Turkey, 22030
    • Novartis Investigative Site
  • Istanbul, Turkey, 34890
    • Novartis Investigative Site
  • Izmir, Turkey, 35040
    • Novartis Investigative Site
  • Samsun, Turkey, 55139
    • Novartis Investigative Site
• United Kingdom
  • Edinburgh, United Kingdom, EH4 2XU
    • Novartis Investigative Site
  • Manchester, United Kingdom, M20 4BX
    • Novartis Investigative Site
  • Nottingham, United Kingdom, NG5 1PB
    • Novartis Investigative Site
  • Hants
    • Portsmouth, Hants, United Kingdom, PO6 3LY
      • 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 Smilow Cancer Hospital
  • 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 Div of Hematology/Oncology
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital .
  • New Jersey
    • Hackensack, New Jersey, United States, 07601
      • Hackensack University Medical Ctr SC
  • 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 Dept.ofUniv.Rochester/JPWilmot
  • Virginia
    • Charlottesville, Virginia, United States, 22903
      • University of Virginia 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

Other protocol-defined Inclusion/Exclusion Criteria may apply.

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
Placebo Comparator: Placebo + Azacitidine; Participants will receive Placebo plus Azacitidine	Drug: Azacitidine; A dose of Azacitidine 75 mg/m2 will be administered IV or subcutaneously (SC) on Day 1-7, or Day 1-5, 8 and 9.; Drug: Placebo; A dose of Placebo 800 mg will be administered intravenously every 4 weeks (Q4W).; Drug: Sabatolimab; A dose of MBG453 800 mg will be administered intravenously (IV) every 4 weeks (Q4W).; Other Names: MBG453
Experimental: MBG453 (Sabatolimab) + Azacitidine; Participants will receive MBG453 plus Azacitidine	Drug: Azacitidine; A dose of Azacitidine 75 mg/m2 will be administered IV or subcutaneously (SC) on Day 1-7, or Day 1-5, 8 and 9.; Drug: Sabatolimab; A dose of MBG453 800 mg will be administered intravenously (IV) every 4 weeks (Q4W).; Other Names: MBG453

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival	Time from randomization until death due to any cause	Up to 5 years after last patient randomized

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 patients. 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 from randomization to at least 3 points worsening from baseline will be presented.	Up to 5 years after last patient randomized
Key secondary endpoint 2: Red Blood Cell transfusion-free intervals	Cumulative times of intervals with no evidence of Red Blood Cell (RBC) transfusion for at least 8 weeks after randomization	Up to 5 years after last patient randomized
Key secondary endpoint: Percent of subjects with at least 3 point confirmed improvement from baseline in FACIT-fatigue scoresscore	FACIT-Fatigue score is a 13-item questionnaire designed to assess fatigue in cancer patients. 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. Percentage of subjects with at least 3 point confirmed improvement from baseline will be presented.	Up to 5 years after last patient randomized
Key secondary endpoint 4: Percent of subjects with at least 10 point confirmed improvement from baseline in physical functioning using European Or ganization 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 patients. Subject's 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. Percentage of subjects with at least 10 point confirmed improvement from baseline in physical functioning will be presented.	Up to 5 years after last patient randomized
Key secondary endpoint 5: Percent of subjects 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 patients. Subject's 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. Percentage of subjects with at least 10 point confirmed improvement from baseline in emotional functioning will be presented.	Up to 5 years after last patient randomized
Percentage of subjects 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 subjects with complete remission (CR), or marrow remission (mCR), or partial remission (PR), or hematologic improvement (HI)	Up to 5 years after last patient randomized
Percentage of subjects with SD in each treatment arm according to International Working Group for MDS (IWG-MDS) as per investigator assessment	Response rate of subjects with stable disease (SD)	Up to 5 years after last patient randomized
Progression Free Survival (PFS)	Time from randomization to disease progression (including transformation to acute leukemia per WHO 2016 classification), relapse from CR according to International Working Group for MDS (IWG-MDS), or death due to any cause, whichever occurs first, as per investigator assessment	Up to 5 years after last patient randomized
Leukemia-free survival	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 5 years after last patient randomized
Number of transfusion dependent subjects at baseline who become Red Blood Cells/platelets transfusion independent after randomization	Improvement in RBC/Platelets transfusion independence as per International Working Group for MDS (IWG-MDS) criteria	Up to 5 years after last patient randomized as per IWG-MDS criteria
Percentage of transfusion dependent subjects at baseline who become Red Blood Cells/platelets transfusion independent after randomization	Improvement in RBC/Platelets transfusion Independence as per International Working Group for MDS (IWG-MDS) criteria	Up to 5 years after last patient randomized
Pharmacokinetics of MBG453 (parameter Cmax)	Maximum (peak) MBG453 concentration [Cmax]	At Day 8 of each cycle (1 cycle = 28 days) until cycle 9, at day 8 of cycle 12 and every 6 cycles thereafter up to 150 day after end of study drug
Pharmacokinetics of MBG453 (parameter AUC)	Area Under the Curve [AUC]	At Day 8 of each cycle (1 cycle = 28 days) until cycle 9, at day 8 of cycle 12 and every 6 cycles thereafter up to 150 day after end of study drug
Anti-drug Antibody (ADA) prevalence at baseline and ADA incidence on-treatment	Immunogenicity of MBG453	At Day 8 of each cycle (1 cycle = 28 days) until cycle 9, at day 8 of cycle 12 and every 6 cycles thereafter up to 150 day after end of study drug
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 will be presented.	Up to 5 years after last patient randomized
Change from baseline in the European Quality of Life (EuroQoL) - 5 Dimensions, 5 Level Questionnaire (EQ-5D-5L) Visual Analogue Scale over time	The EQ-5D-5L VAS records the subject'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 will be presented.	Up to 5 years after last patient randomized
Change from baseline to C12D1 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 patients. Subject'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 will be 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

Study record dates

Study Major Dates

• Study Start (Actual): June 8, 2020
• Primary Completion (Estimated): September 17, 2024
• Study Completion (Estimated): September 17, 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 (Actual): March 20, 2024
• Last Update Submitted That Met QC Criteria: March 19, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: Phase III; chronic myelomonocytic leukemia; MDS; TIM-3; MBG453; myelodysplastic syndrome; azacitidine; CMML-2; Sabatolimab
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms by Histologic Type; Neoplasms; Disease Attributes; Disease; Bone Marrow Diseases; Hematologic Diseases; Precancerous Conditions; Myelodysplastic-Myeloproliferative Diseases; Leukemia, Myeloid; Chronic Disease; Syndrome; Myelodysplastic Syndromes; Leukemia; Preleukemia; Leukemia, Myelomonocytic, Chronic; Leukemia, Myelomonocytic, Juvenile; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Azacitidine
• 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 patients who have participated in the trial in line with applicable laws and regulations.

Drug and device information, study documents

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