Using MBG453 to treat lower-risk myelodysplastic syndromes

TIM3 Inhibition With MBG453 for Patients With Lower Risk MDS: an Adaptive Two-Stage Phase II Clinical Trial

This study is testing a new drug called MBG453 to see if it can help people with lower-risk myelodysplastic syndromes who haven't had success with standard treatments.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 20 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Massachusetts General Hospital (Academic / other)
• Drugs / interventions: chemotherapy, prednisone
• Locations: 3 sites (Boston, Massachusetts and 2 other locations)
• Trial ID: NCT04823624 on ClinicalTrials.gov

What this trial studies

This clinical trial evaluates the effectiveness of MBG453, a humanized monoclonal antibody, in patients with lower-risk myelodysplastic syndromes (MDS) who are not responding to or are intolerant of standard therapies. The trial employs an adaptive two-stage design to assess the drug's activity, focusing on patients with specific eligibility criteria related to their MDS condition. Participants will receive treatment as long as they benefit from the drug, with follow-up assessments conducted for 12 months post-treatment. The study aims to enroll approximately 20 individuals.

Who should consider this trial

Good fit: Ideal candidates include adults aged 18 and older with lower-risk MDS who have progressed on or are intolerant to prior therapies.

Not a fit: Patients with higher-risk MDS or those who are not eligible for the specified inclusion criteria may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a new therapeutic option for patients with lower-risk MDS who have limited treatment alternatives.

How similar studies have performed: While MBG453 has been approved for other uses, this specific application in MDS is novel and has not been extensively tested in prior studies.

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 mg/dL)
  * 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 trial.
* 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.

Where this trial is running

Boston, Massachusetts and 2 other locations

• Massachusetts General Hospital Cancer Center — Boston, Massachusetts, United States (Recruiting)
• Brigham and Women's Hospital — Boston, Massachusetts, United States (Not_yet_recruiting)
• Dana-Farber Cancer Institute — Boston, Massachusetts, United States (Not_yet_recruiting)

Study contacts

• Principal investigator: Andrew Brunner, MD — Massachusetts General Hospital
• Study coordinator: Andrew Brunner, MD

Conditions Myelodysplastic Syndromes