MGNX

Margetuximab

HER2-positive metastatic breast cancer

PDUFA

Exp Date

December 18, 2020

Amp Volatility Score

N/A

Catalyst Info & Data Links

POSTERS

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MECHANISM OF ACTION / RATIONALE

  • Margetuximab is an investigational monoclonal antibody that targets HER2-expressing tumors, including certain types of breast and gastroesophageal cancers. HER2 is critical for the growth of many types of tumors. Using MacroGenics’ Fc Optimization platform, the constant region (Fc region) of margetuximab was engineered to increase its ability to kill tumor cells through an Fc-dependent mechanism, including antibody dependent cell-mediated cytotoxicity (ADCC). Margetuximab is currently being studied as a potential treatment for HER2-positive metastatic breast cancer and advanced gastric cancer.

  • Using MacroGenics’ Fc Optimization platform, the constant region (Fc region) of margetuximab was engineered to increase its ability to kill tumor cells through an Fc-dependent mechanism, including ADCC. Specifically, margetuximab’s ability to bind to activating Fc-gamma receptors was increased and its ability to bind to the Fc-gamma inhibitory receptor on immune effector cells, including monocytes, macrophages, dendritic cells and natural killer, or NK, cells, was decreased. As a result, margetuximab may have the potential to be effective in a broader population than is currently treated with trastuzumab and may overcome resistance in populations that no longer respond to trastuzumab. (Learn More: Fc Optimization Platform)

  • Margetuximab is believed to mediate its therapeutic activity against HER2+ tumors by a combination of mechanisms including:

  • Modulation of HER2 signaling, resulting in growth retardation or the induction of apoptosis, or cell death;

  • ADCC and improved binding to immune cells to enhance destruction of HER2+ tumor cells; and

  • Presentation of tumor antigens by cells such as macrophages that take up and display the antigens to other cells of the immune system, including T cells.

Updated by HC

MGNX, Margetuximab, cancer, oncology, breast cancer, cancer, breast, HER2,  metastatic

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