Orphan drug designation granted to GBR 1342

The United States (US) Food & Drug Administration (FDA) have granted GBR 1342 orphan drug designation (ODD) for the treatment of multiple myeloma (MM).^1,2 The maximum tolerated dose (MTD) of GBR 1342 is currently being investigated in an open-label, phase I trial, H2 CY 2019.^1,3 The 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.^1,3 This 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^st June 2018 in the Journal of Clinical Oncology.⁵ This is a first-in-human trial (NCT03309111):⁶

• Patients enrolled have relapsed/refractory disease⁵
  • More than three prior lines of therapy⁵
• 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 MTD⁵
  • The study has enrolled patients in cohorts one–nine with enrollment continuing in cohort 10⁵
    • 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 schedule⁵
• Part two of the study will treat 65 patients at the MTD until disease progression or unacceptable toxicity⁵
• 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