A Phase II efficacy and safety study of MBG453 in combination with hypomethylating agents in subjects with IPSS-R intermediate, high or very high risk myelodysplastic syndrome (MDS).

Phase 1

• Conditions: Adult subjects with intermediate, high or very high risk myelodysplastic syndrome (MDS) as per IPSS-R criteria; MedDRA version: 20.0Level: HLTClassification code 10028536Term: Myelodysplastic syndromesSystem Organ Class: 100000004851; Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2018-004479-11-BE
• Lead Sponsor: ovartis Pharma AG

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2019-07-11
• Last Update Posted: 29 July 2024

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 120

Inclusion Criteria

1. Signed informed consent must be obtained prior to participation in the study.
2. Age = 18 years at the date of signing the informed consent form (ICF).
3. Morphologically confirmed diagnosis of a myelodysplastic syndrome (MDS) based on 2016 WHO classification (Arber et al 2016) by investigator assessment with one of the following Prognostic Risk Categories, based on the International Prognostic Scoring System (IPSS-R):
• Very high (> 6 points)
• High (> 4.5-6 points)
• Intermediate (> 3-4.5 points): a subject determined to be in the Intermediate Prognostic Risk Category is only allowable in the setting of = 5% bone marrow blast
4. Not eligible at the time of screening, for intensive chemotherapy according to the investigator, based on local standard medical practice and institutional guidelines for treatment decisions.
5. Not eligible at the 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.
6. Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2.
Refer to protocol for complete list of inclusion criteria.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 36
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 84

Exclusion Criteria

1. Prior exposure to TIM-3 directed therapy at any time. Prior therapy with immune check point inhibitors (e.g. anti-CTLA4, anti-PD-1, anti-PDL1, or anti-PD-L2), cancer vaccines are allowed except if the drug was administered within 4 months prior to randomization.
2. Previous first-line treatment for intermediate, high or very high risk myelodysplastic syndromes (based on IPSS R) with chemotherapy or any other antineoplastic agents including lenalidomide and hypomethylating agent (HMAs) such as decitabine or azacitidine.
3. History of severe hypersensitivity reactions to any ingredient of the study treatment (azacitidine, decitabine or MGB453) or their excipients, or to monoclonal antibodies (mAbs).
4. Currently using or used within 14 days prior to randomization 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.
5. Investigational treatment for MDS received within 4 weeks prior to randomization. In case of a checkpoint inhibitor: 4 months minimum prior to randomization interval is necessary to allow enrollment.
6. Active autoimmune disease requiring systemic therapy (e.g. corticosteroids).
7. Live vaccine administered within 30 days prior to randomization.
Refer to protocol for complete list of exclusion criteria.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified