The Food and Drug Administration (FDA) has approved Margenza (margetuximab-cmkb; MacroGenics) in combination with chemotherapy, for the treatment of adult patients with metastatic HER2-positive breast cancer who have received 2 or more prior anti-HER2 regimens, at least 1 of which was for metastatic disease.

Margetuximab is an Fc-engineered, monoclonal antibody that targets the HER2 oncoprotein. The approval was based on the phase 3 SOPHIA trial, which compared margetuximab plus chemotherapy to trastuzumab plus chemotherapy in 536 patients with HER2-positive metastatic breast cancer, who have previously been treated with anti-HER2-targeted therapies.  Results showed that the objective response rate for margetuximab plus chemotherapy was 22% compared with 16% for trastuzumab plus chemotherapy.

There was a statistically significant 24% reduction in the risk of disease progression or death in the margetuximab-treated group compared with trastuzumab (HR=0.76; 95% CI, 0.59-0.98; P =.033; median PFS 5.8 vs 4.9 months). The final Overall Survival analysis is expected in the second half of 2021.

Margenza carries a Boxed Warning for left ventricular dysfunction and embryo-fetal toxicity. Regarding adverse reactions, the trial found that those with over 20% occurrence included fatigue/asthenia (57%), nausea (33%), diarrhea (25%), and vomiting (21%). In addition, infusion related reactions (IRRs) occurred in 13% of patients treated with margetuximab, with the majority reported as Grade 2 or less. Grade 3 IRRs occurred in 1.5% of patients. 

The Company expects Margenza to be available in March 2021.

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MacroGenics Announces FDA Approval of MARGENZA™ for Patients with Pretreated Metastatic HER2-Positive Breast Cancer. [press release]. Rockville, MD: MacroGenics; December 17, 2020.