Phase II MBG453 for MDS adult patients

  • Research type

    Research Study

  • Full title

    A randomized, double-blind, placebo-controlled phase II multi-center study of intravenous MBG453 added to hypomethylating agents in adult subjects with intermediate, high or very high risk myelodysplastic syndrome (MDS) as per IPSS-R criteria

  • IRAS ID

    263253

  • Contact name

    Daniel Wiseman

  • Contact email

    daniel.wiseman@manchester.ac.uk

  • Sponsor organisation

    Novartis Pharma AG

  • Eudract number

    2018-004479-11

  • Clinicaltrials.gov Identifier

    NCT03946670

  • Duration of Study in the UK

    3 years, 6 months, days

  • Research summary

    Research Summary:
    It is estimated that 15,000 to 20,000 new cases of Myelodysplastic Syndromes (MDS) are diagnosed annually in the USA (Klepin 2016). The incidence of MDS is more frequent in male patients and increases with age, with a median age at diagnosis of about 70 years.

    Current treatment guidelines for MDS recommend modification of the disease with hematopoietic stem cell transplantation (HSCT, treatment with a curative intent), hypomethylating agents (HMA: azacitidine or decitabine) or intensive chemotherapy (Fenaux et al 2014). Choice of therapy is mainly driven by the IPSS-R score, the overall general health status and clinical assessment of comorbidities.

    HMAs have improved outcomes for patients with intermediate/high risk/very high risk MDS; especially for patients who are not candidates for intensive chemotherapy regiments or HSCT. However, despite these improvements, prognosis for patients treated with HMA remains poor. Treatment failure, relapse and transformation to acute myeloid leukemia (AML) are frequent events. Once a patient with higher risk MDS has failed treatment with HMAs or has transformed to AML, survival generally will not exceed 6 months. Thus, improved treatments in addition to HMA and/or as an alternative to HMAs are urgently needed in this patient population.

    The treatment being investigated in this study, the anti-TIM-3 monoclonal antibody MBG453 is a novel checkpoint inhibitor with promising activity in AML and MDS. The purpose of the current study is to assess clinical effects of MBG453 in combination with HMA (azacitidine or decitabine) in adult subjects with IPSS-R intermediate, high, very high risk MDS. The justification for a double blind randomized placebo-controlled trial is to determine the efficacy of adding MBG453 to the current standard of care on the primary efficacy endpoints (complete remission and progression free survival).

    The aim is to recruit 4 patients in 3 UK sites.

    Lay summary of study results:
    “The English lay summary will be available one year post global LPLV (15/07/2025). It will be available to PIs to share with patients and posted in the public domain on Novartis public website
    https://www.novctrd.com/#/

  • REC name

    London - West London & GTAC Research Ethics Committee

  • REC reference

    19/LO/0991

  • Date of REC Opinion

    14 Aug 2019

  • REC opinion

    Further Information Favourable Opinion