A Study of Sabatolimab in Combination With Azacitidine and Venetoclax in High or Very High Risk MDS Participants

NCT04812548 | Terminated Phase 2 Results FDA Drug

• 2 other identifiers: CMBG453B122032020-003669-21
• Study Type: interventional
• Target: 20
• Locations: 7 countries
• Sites: 10

Brief Summary

The purpose of the study was to find out if the new drug sabatolimab when given in combination with azacitidine and venetoclax, was safe and had beneficial effects in participants with high or very high risk myelodysplastic syndrome (MDS) who were not suitable for treatment with intensive chemotherapy or a stem-cell transplant (HSCT).

Conditions

Myelodysplastic Syndrome (MDS)

Keywords

MGM453; Phase II; sabatolimab; TIM-3; venetoclax; azacitidine; Myelodysplastic syndrome; MDS

Outcome Measures

Primary Outcomes (2)

• Rate of Dose Limiting Toxicities (DLTs) - All Grades (Safety run-in Patients Only)

  A dose-limiting toxicity (DLT) is defined as an adverse event or abnormal laboratory value considered by the Investigator to be at least possibly related to sabatolimab as a single contributor or in combination with other component(s) of study treatment that occurs during the DLT observation period and meets severity criteria as per protocol.

  From Cycle 1 Day 8 to end of Cycle 2 (Cycle = 28 Days)

• Percentage of Participants (Receiving 800mg Sabatolimab) Achieving Complete Remission (CR) Per Investigator Assessment

  This endpoint assessed Complete Remission (CR) Rate of participants from Cohort 2 of Part 1 and Part 2 according to Investigator assessment per modified IWG-MDS - Cheson 2006 criteria. CR is defined as follows: bone marrow blasts \<=5%, hemoglobin level ≥ 10 g/dL, platelets count ≥ 100\*10\^9/L, neutrophils count ≥ 1.0\*10\^9/L, absence of blasts in peripheral blood.

  up to approx. 23 months

Secondary Outcomes (16)

• Percentage of Subjects Achieving a Complete Remission (CR) + Morphologic Complete Remission (mCR): Safety run-in (Part 1)

  up to approx. 23 months

• Overall Response Rate (ORR) of Participants Who Achieved Hematologic Improvement (HI) or Better as Best Response

  up to approx. 23 months

• Percentage of Participants Who Are RBC/Platelets Transfusion Independent

  up to approx. 23 months

• Duration of Transfusion Independence

  up to approx. 23 months

• Peak Serum Concentration (Cmax) of Sabatolimab

  Continuously collected for patients during treatment with sabatolimab up to 150 days after last treatment, approx. 23 months

Study Arms (1)

sabatolimab + azacitidine + venetoclax

EXPERIMENTAL

Part 1: Safety run-in consisted of 2 subsequent cohorts of a lower dose (cohort 1) and a higher dose (cohort 2) of sabatolimab in combination with fixed dose of venetoclax and azacitidine. Part 2 (did not start as recruitment was stopped in Part 1) Expansion was to enroll additional participants to further investigate the regimen including sabatolimab at the higher dose, azacitidine and venetoclax. Participants data from Part 1 and Part 2 treated with the higher dose was to have been combined to determine the complete remission rate.

Drug: sabatolimab; Drug: azacitidine; Drug: venetoclax

Interventions

sabatolimab DRUG

Sabatolimab was administered at a low dose (Safety run-in (Part 1) cohort 1) or a high dose (Safety run-in (Part 1) cohort 2) via i.v. infusion over 30 minutes on Day 8 of every treatment cycle. Cycle = 28 days

Also known as: MBG453

sabatolimab + azacitidine + venetoclax

azacitidine DRUG

A standard dose of azacitidine was given subcutaneously or intravenously every day for seven consecutive days on days 1-7 of a confirmed treatment cycle. In keeping with standard clinical practice, the alternative schedules for five consecutive days on days 1-5, followed by a two day break, then two consecutive days on days 8-9 was permitted (alternative schedule).

sabatolimab + azacitidine + venetoclax

venetoclax DRUG

Venetoclax film-coated tablets was administered at a dose of 400 mg orally or corresponding reduced dose for concomitant use with P-gp inhibitors or moderate or strong CYP3A4 inhibitors, once a day, from C1D1 to C1D14 during the treatment cycle. No ramp-up for venetoclax was necessary.

sabatolimab + azacitidine + venetoclax

Eligibility Criteria

• Age: 18 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 myelodysplastic syndrome (MDS) based on 2016 WHO 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) (Greenberg et al 2012):
• Very high (\> 6 points)
• High (\> 4.5-6 points)
• Not immediately eligible for hematopoietic stem-cell transplantation (HSCT) or intensive chemotherapy at the time of screening due to individual clinical factors such as age, comorbidities and performance status, donor availability (de Witte et al 2017)
• Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2

You may not qualify if:

• Prior exposure to TIM-3 directed therapy or any BCL-2 inhibitor (including venetoclax) at any time
• Prior therapy with immune check point inhibitors (e.g. anti-CTLA4, anti-PD-1, anti-PD-L1, or anti-PD-L2) or cancer vaccines is not allowed if the last dose of the drug was administered within 4 months prior to start of treatment
• Previous first-line treatment for very high risk or high risk myelodysplastic syndromes (based on IPSS-R,Greenberg et al 2012 and Arber et al, 2016) with any antineoplastic agents, approved or investigational, including for example chemotherapy, lenalidomide and hypomethylating agents (HMAs) such as decitabine or azacitidine However, a one single cycle of HMAs treatment only started prior to enrollment is allowed.
• Live vaccine administered within 30 days prior to start of treatment
• Current use or use within 14 days prior to start of treatment 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
• History of severe hypersensitivity reactions to any ingredient of study drug(s) (azacitidine, venetoclax or sabatolimab) or monoclonal antibodies (mAbs) and/or their excipients
• Participants with Myelodysplastic syndrome (MDS) based on 2016 WHO classification (Arber et al, 2016) with revised International Prognostic Scoring System (IPSS-R) ≤ 4.5

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (10)

Novartis Investigative Site

Brasschaat, 2930, Belgium

Location

Novartis Investigative Site

Marseille, 13273, France

Location

Novartis Investigative Site

Nice, 06202, France

Location

Novartis Investigative Site

Düsseldorf, 40479, Germany

Location

Novartis Investigative Site

Stuttgart, 70376, Germany

Location

Novartis Investigative Site

Alexandroupoli, Evros, 681 00, Greece

Location

Novartis Investigative Site

Pátrai, 265 00, Greece

Location

Novartis Investigative Site

Nyíregyháza, 4400, Hungary

Location

Novartis Investigative Site

Genova, GE, 16132, Italy

Location

Novartis Investigative Site

Barcelona, Catalonia, 08036, Spain

Location

MeSH Terms

Conditions

Myelodysplastic Syndromes

Interventions

sabatolimab; Azacitidine; venetoclax

Condition Hierarchy (Ancestors)

Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

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

Results Point of Contact

• Title: Clinical Disclosure Office
• 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 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 23, 2021
• First Posted: March 23, 2021
• Study Start: May 31, 2021
• Primary Completion: May 8, 2023
• Study Completion: May 8, 2023
• Last Updated: October 9, 2025
• Results First Posted: June 11, 2024

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will share

Locations

ES (1); HU (1); GR (2); DE (2); IT (1); FR (2); BE (1)