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Author: Sandra Cuellar
Date: Sept. 2021
From: Oncology(Vol. 35, Issue 9)
Publisher: Intellisphere, LLC
Document Type: Interview
Length: 1,350 words
Lexile Measure: 1150L

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Q: Can you briefly describe margetuximab's mechanism of action?

A: The mechanism of action of margetuximab [Margenza] is exciting; 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; now, we've advanced to antibody-drug conjugates, where we're tacking on a cytotoxic component, and 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 [NK] cell. What's exciting about this mechanism of action is that we're building on this technology with 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 NK cell. When it binds to the NK cell, the idea is that you're enhancing the antibody-dependent cellular cytotoxicity. 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 afinity to that receptor, which is different from pertuzumab [Perjeta].

Q: What are some of the concerns with margetuximab's toxicity profile? Have any new safety concerns become more apparent with its use in the real-world treatment setting?

A: Margetuximab is an antibody that targets HER2. Two things are really important to highlight about the safety profile of margetuximab that were observed in the SOPHIA trial [NCT02492711]. First, the infusion-related reactions: About 13% of patients in SOPHIA experienced infusion-related reactions, primarily grade 1 and grade 2 [in...

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Gale Document Number: GALE|A679525840