Sandra Cuellar, PharmD, BCOP, FASHP, Discusses the Mechanism of Action of Margetuximab for HER2-Positive Metastatic Breast Cancer

For the latest installment of the “Product Profile” in the journal ONCOLOGY®, Sandra Cuellar, PharmD, BCOP, FASHP, of the University of Illinois College of Pharmacy, spoke about the mechanism of action of margetuximab (Margenza), which is approved for use in patients with HER2-positive metastatic breast cancer following 2 or more prior lines of anti-HER2 therapy, with at least 1 being in the metastatic setting.

Transcript:

The mechanism of action of margetuximab [Margenza] is exciting and I think we’re now moving into this new era of monoclonal antibody technology. We’ve been using monoclonal antibodies since the 1990s, and the way I teach [about] them in school is [that there are] naked monoclonal antibodies, the first ones at least; then we’ve advanced to antibody-drug conjugates, where we’re tacking on a cytotoxic component. Now we’ve gone to bispecific monoclonal antibodies [that] have dual binding. When we talk about the mechanism of action of margetuximab, it’s a bispecific monoclonal antibody, and it has 2 binding sites. It has one binding that targets the HER2 receptor. It’s been genetically modified and engineered to bind to the natural killer cell. What’s exciting about this mechanism of action is that we’re building on this technology, and we have this dual binding so we’re enhancing this basic monoclonal antibody that we’ve been using, at least with trastuzumab [Herceptin], since the 1990s.

More specifically, the mechanism of action of margetuximab is that it targets the HER2 receptor, the extracellular domain, and the FC [fragment crystallizable] component of that monoclonal antibody has been genetically engineered to target and bind to the natural killer cell. When it binds to the natural killer cell, the ideas that you’re enhancing the antibody-dependent cellular cytotoxicity [ADCC]. Margetuximab has the same binding, as well as binding affinity, to the HER2 receptor as trastuzumab. We have 2 monoclonal antibodies, trastuzumab and margetuximab, binding to the same site with a similar binding affinity to that receptor which is different than pertuzumab [Perjeta].