Clinical Trials /

MBG453 in Lower Risk MDS



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.

Related Conditions:
  • Chronic Myelomonocytic Leukemia
  • Myelodysplastic Syndromes
Recruiting Status:

Not yet recruiting


Phase 2

Trial Eligibility



  • Brief Title: MBG453 in Lower Risk MDS
  • Official Title: TIM3 Inhibition With MBG453 for Patients With Lower Risk MDS: an Adaptive Two-Stage Phase II Clinical Trial

Clinical Trial IDs

  • ORG STUDY ID: 20-637
  • NCT ID: NCT04823624


  • Myelodysplastic Syndromes




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.

Detailed Description

      This is an adaptive two-stage phase II clinical trial to assess the activity of the
      anti-TIM-3, (T cell immunoglobulin domain and mucin domain) antibody, MBG453, in patients
      with lower-risk myelodysplastic syndromes (MDS), not eligible for or progressing on frontline

      The U.S. Food and Drug Administration (FDA) has not approved MBG453 for myelodysplastic
      syndromes (MDS), but it has been approved for other uses.

      The study drug (MBG453) may interact with TIM-3 (an antibody which is a protein that attaches
      to foreign infectious/invading cells and signals the immune system) which might aid the
      immune system's response by helping immune cells recognize, find, and destroy cancer cells in
      the body.

      The research study procedures include screening for eligibility and study treatment,
      including evaluations and follow up visits.

      Participants will receive study treatment for as long as they and their doctor believe they
      are benefiting from the study drug. Participants will then be followed for 12 months after
      their last dose of the study drug or until they withdraw their consent to be contacted.

      It is expected that about 20 people will take part in this research study

Trial Arms

MG MBG453ExperimentalParticipants will be given MBG453 On Day 1 of each cycle 28 days (4 weeks) study cycle
  • MBG453

Eligibility Criteria

        Inclusion Criteria:

          -  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

               -  AST(SGOT)/ALT(SGPT) ≤3 × institutional ULN

               -  Creatinine clearance ≥30 mL/min/1.73 m2 (by MDRD calculation)

          -  Human immunodeficiency virus (HIV)-infected participants on effective anti-retroviral
             therapy with undetectable viral load over the prior 6 months are eligible for this

          -  Participants with known history or current symptoms of cardiac disease, or history of
             treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac
             function using the New York Heart Association Functional Classification. To be
             eligible for this trial, participants should be class 2B or better.

          -  Ability to understand and the willingness to sign a written informed consent document.

        Exclusion Criteria:

          -  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.

          -  Prior solid organ transplant is exclusionary. Patients with prior hematopoietic cell
             transplant are eligible if they are over 6 months from transplant and not on any
             related immunosuppressive therapy.

          -  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:

               -  The following will not be exclusionary: non-melanoma skin cancer, noninvasive
                  colonic polyps, superficial bladder tumors, cervical cancer in-situ, ductal
                  carcinoma in situ of the breast, monoclonal B-cell lymphocytosis, or monoclonal
                  gammopathy of undetermined significance.

               -  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.
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Overall response rate (ORR)
Time Frame:6 months
Safety Issue:
Description: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.

Secondary Outcome Measures

Measure:Number of Participants With Treatment-Related Adverse Events as Assessed by CTCAE Version 5.0
Time Frame:during the intervention, an average of 1 year
Safety Issue:
Description:The number and proportion of adverse events, graded as defined by CTCAE version 5.0 will be tabulated by type and grade.
Measure:Overall survival (OS) 1-year
Time Frame:1 year
Safety Issue:
Description:Estimated using the Kaplan and Meier method.
Measure:Progression free survival (PFS)
Time Frame:through study completion, an average of 1 year
Safety Issue:
Description:Estimated using the Kaplan and Meier method.
Measure:Time to disease progression
Time Frame:through study completion, an average of 1 year
Safety Issue:
Description:Estimated using the Kaplan and Meier method.
Measure:Duration of response
Time Frame:through study completion, an average of 1 year
Safety Issue:
Description:Estimated using the Kaplan and Meier method.


Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Massachusetts General Hospital

Trial Keywords

  • Myelodysplastic Syndromes

Last Updated

April 1, 2021