MBG453 in Lower Risk MDS

NCT04823624 | Terminated Phase 2 Results DMC FDA Drug

• 1 other identifier: 20-637
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 3

Brief Summary

This research study is assessing the efficacy of MBG-453, a humanized monoclonal antibody, in treating myelodysplastic syndromes (MDS). The name of the study drug involved in this study is MBG453.

Conditions

Myelodysplastic Syndromes

Keywords

Myelodysplastic Syndromes

Outcome Measures

Primary Outcomes (1)

• Overall Response Rate (ORR)

  Assessed on the proposal for the modification of the International Working Group (IWG) response criteria in myelodysplasia (Cheson et al., 2006), but modified to include complete remission with partial hematologic improvement CRh (Bloomfield et al., 2018), and the 2018 proposed update for hematologic responses and transfusion independence (TI) (Platzbecker et al., 2019). Patients with dysplastic-type CMML will use MDS risk-stratification and response assessment criteria.

  6 months

Secondary Outcomes (5)

• Number of Participants With Treatment-Related Adverse Events as Assessed by CTCAE Version 5.0

  during the intervention, an average of 1 year

• Overall Survival (OS) 1-year

  1 year

• Progression Free Survival (PFS)

  through study completion, an average of 1 year

• Time to Disease Progression

  through study completion, an average of 1 year

• Duration of Response

  through study completion, an average of 1 year

Study Arms (1)

MG MBG453

EXPERIMENTAL

Participants will be given MBG453 On Day 1 of each cycle 28 days (4 weeks) study cycle

Drug: MBG453

Interventions

MBG453 DRUG

intravenous infusion

MG MBG453

Eligibility Criteria

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

You may qualify if:

• Lower risk MDS patients (IPSS-R score ≤ 3.5 at diagnosis) who have progressed or are refractory to/intolerant of prior therapy and meet one of the following categories:
• RBC transfusion dependent according to IWG criteria must either be unresponsive to prior ESA therapy or have an EPO level \> 500
• Prior HMA therapy
• Patients with the following cytopenias who otherwise are felt to require treatment per the treating physician:
• Platelets \< 50k/uL
• ANC \< 500 cells/uL
• Patients with MDS with isolated del(5q) ("5q- syndrome") must have progressed on or not tolerated lenalidomide
• Patients who are not felt to be candidates for or lack other standard treatment options. Patients with prior luspatercept exposure are eligible.
• Patients with dysplastic type CMML (WBC \< 13,000 cells/uL) meeting the above criteria are eligible; responses will be assessed using MDS criteria
• Age ≥18 years. Because no dosing or adverse event data are currently available on the use of MGB453 in participants \<18 years of age, children are excluded from this study, but will be eligible for future pediatric trials.
• ECOG performance status ≤2 (see Appendix A).
• Participants must have adequate organ and marrow function as defined below within 21 days of treatment:
• Total bilirubin ≤ 2 mg/dL (unless due to Gilbert's in which case it must be \<3 mg/dL)
• AST(SGOT)/ALT(SGPT) ≤3 × institutional ULN
• Creatinine clearance ≥30 mL/min/1.73 m2 (by MDRD calculation)

You may not qualify if:

• Participants who have had chemotherapy or radiotherapy within 14 days or five half-lives, whichever is shorter, prior to the first dose of study treatment.
• Participants who are receiving any other investigational agents; a washout of 14 days or 5 half-lives, whichever is longer, is required. The washout period for biologic agents should be 28 days since the last dose.
• Prior exposure to a TIM-3 inhibitor.
• Active autoimmune disease requiring \> 10 mg per day of prednisone or the equivalent. Inactive or controlled autoimmune disease is allowed.
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to MBG453.
• Active untreated or concurrent malignancy that is distinct in primary site or histology, excluding:
• Hormonal therapy is allowed.
• History of other malignancy is allowed if not requiring active management.
• Other malignancies that were treated with curative intent at least 1 year prior to study screening and without evidence of active disease will be allowed.
• Participants with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial pending discussion with the principal investigator.
• Participants with uncontrolled intercurrent illness.
• Participants must not have clinically active HBV or HCV; testing is not required
• Receipt of a live vaccination within 28 days of cycle 1 day 1
• Participants with psychiatric illness/social situations that would limit compliance with study requirements.
• Female contraception is required. Pregnant women are excluded from this study because MBG453 is an agent with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with MBG453, breastfeeding should be discontinued. Women of child-bearing potential should use highly effective methods of contraception during treatment and for 150 days after the last dose of MBG453.

Sponsors & Collaborators

• Massachusetts General Hospital: lead
• Novartis: collaborator

Study Sites (3)

Massachusetts General Hospital Cancer Center

Boston, Massachusetts, 02114, United States

Location

Brigham and Women's Hospital

Boston, Massachusetts, 02215, United States

Location

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

MeSH Terms

Conditions

Myelodysplastic Syndromes

Interventions

sabatolimab

Condition Hierarchy (Ancestors)

Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases

Limitations and Caveats

The trial closed early due to changes in support for the study drug. Patients continue in follow up off treatment and correlative studies continue on the subset of patients who were enrolled prior to closure.

Results Point of Contact

• Title: Andrew Brunner, MD
• Organization: Massachusetts General Hospital

abrunner@mgh.harvard.edu

617-724-1124

Study Officials

• Andrew Brunner, MD

  Massachusetts General Hospital

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: March 9, 2021
• First Posted: April 1, 2021
• Study Start: January 27, 2022
• Primary Completion: November 12, 2024
• Study Completion: November 1, 2025
• Last Updated: February 27, 2026
• Results First Posted: February 27, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Data can be shared no earlier than 1 year following the date of publication
• Access Criteria: Contact the Partners Innovations team at http://www.partners.org/innovation

Locations

US (3)