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Orphan drug designation granted to GBR 1342

Sep 19, 2019

The United States (US) Food & Drug Administration (FDA)have granted GBR 1342 orphan drug designation (ODD) for the treatment of multiple myeloma (MM). 1,2The maximum tolerated dose (MTD) of GBR 1342 is currently being investigated in an open-label, phase I trial, H2 CY 2019. 1,3The trial will evaluate biomarkers, immunogenicity and disease activity. 1

About GBR 1342

GBR 1342 is created using “bispecific engagement by antibodies based on T-cell receptor” (BEAT®) technology. 1,3This method of producing bispecific antibodies is designed to create products with a low immunogenicity profile.

GBR 1342 is a bispecific monoclonal antibody that binds two targets; CD3 on T-cells and CD38 on target tumor cells. It subsequently induces T-cell activation and directs them to kill CD38 +tumor cells. 1,3

CD38 is a glycoprotein with ectoenzymatic functions which is highly expressed on MM cells, cells of hematopoietic origin and in solid tumors. One advantage of anti-CD38 therapy therefore, is that it may have a role across different malignancies. However, since CD38 is also expressed on non-malignant hematopoietic cells such as natural killer (NK) cells, B-cells and activated T-cells, it may also have adverse effects on the activity of normal cells. 4

Phase I trial: H2 CY 2019 3,5,6

The first report from the phase I study was published on 1 stJune 2018 in the Journal of Clinical Oncology . 5This is a first-in-human trial ( NCT03309111): 6

  • Patients enrolled have relapsed/refractory disease 5
    • More than three prior lines of therapy 5
  • This is a two-part study, aiming to: 6
  1. Investigate the safety and the MTD of GBR 1342 as monotherapy
  2. Further analyze safety, tolerability and preliminary clinical activity at the MTD
  • In part one, GBR 1342 is administered as an intravenous infusion on Day one and Day 15 of each 28-day cycle, at escalating dose levels, to determine the MTD 5
    • The study has enrolled patients in cohorts one–nine with enrollment continuing in cohort 10 5
      • Cohorts one–four consisted of a single subject
      • Cohorts five onwards used a 3+3 enrollment
    • The company responsible for the development of the drug, plan to include a weekly dosing regimen in this study, in addition to the current bi-weekly schedule 5
  • Part two of the study will treat 65 patients at the MTD until disease progression or unacceptable toxicity 5
  • The primary outcome measures of the trial are frequency and severity of adverse events (AEs), number of dose-limiting toxicities and determination of the MTD (part one) and objective response rate (part two) 5,6
  1. Glenmark Receives Orphan Drug Designation for GBR 1342, a Bispecific Antibody Candidate Under Evaluation for the Treatment of Multiple Myeloma.[Accessed 2019 Sep 18]
  2. FDA: Search orphan drug designations and approvals.[Accessed 2019 Sep 18]
  3. Glenmark Pharma.[Accessed 2019 Sep 18]
  4. Morandi F. et al.CD38: A Target for Immunotherapeutic Approaches in Multiple Myeloma. Frontiers in Immunology. 2018 Nov 28. DOI: 10.3389/fimmu.2018.02722
  5. Richter J. R. et al. Phase 1, multicenter, open-label study of single-agent bispecific antibody t-cell engager GBR 1342 in relapsed/refractory multiple myeloma. J Clin Onc. 2018 Jun 01. DOI: 10.1200/JCO.2018.36.15_suppl.TPS3132
  6. Study of GBR 1342, a CD38/CD3 Bispecific Antibody, in Subjects With Previously Treated Multiple Myeloma.[Accessed 2019 Sep 18]