Margenza (margetuximab-cmkb), in combination with chemotherapy, has been approved in the U.S. to treat adults with metastatic HER2-positive breast cancer who have previously received two or more anti-HER2 regimens, at least one of which was for metastatic disease.
The therapy is expected to be launched in the U.S. in March, said the therapy’s developer, MacroGenics.
“The approval of MARGENZA is an exciting milestone for MacroGenics and, more importantly, it brings a new treatment option to metastatic breast cancer patients,” Scott Koenig, MD, PhD, company president and CEO, said in a press release.
In some breast cancers, abnormal activity of the protein HER2 helps to drive cancer growth, and these cancers are referred to as HER2-positive. Because HER2 drives cancer growth in these tumors, blocking the activity of this protein can limit cancer growth and even kill cancer cells.
Several HER2-targeting therapies have previously been approved to treat HER2-positive tumors, including Herceptin (trastuzumab), Perjeta (pertuzumab), and Kadcycla (ado-trastuzumab emtansine). Although these therapies have some differences, all of them utilize antibodies that specifically bind to HER2.
HER2-targeting therapies for breast cancer can significantly improve outcomes (i.e., survival), but some patients will have their disease return after treatment. In these individuals, the cancer typically responds poorly to additional treatments that target HER2.
Margenza is a HER2-targeting antibody that has been designed to more effectively trigger an immune response against cancer cells, which is expected to improve the outcomes of people who have already received multiple HER2-targeted treatments.
The approval of Margenza by the U.S. Food and Drug Administration was based on data from the Phase 3 SOPHIA clinical trial (NCT02492711). This MacroGenics-sponsored trial included 536 patients across nearly 200 sites in the U.S., Canada, Europe, and Asia. All of the participants had previously been treated with Herceptin and Perjeta for their metastatic breast cancer, with 90% also given Kadcycla.
The trial participants were randomized to receive either Margenza or Herceptin, in addition to standard chemotherapy.
Results showed that Margenza significantly improved progression-free survival (PFS) — the time patients lived without evidence of their cancer growing. Compared to Herceptin, Margenza reduced the risk of death or disease progression by 24% — median PFS time was 5.8 months with Margenza and 4.9 months with Herceptin.
In a subset of individuals who usually respond poorly to Herceptin and other antibodies — those with an immune-related genetic variation called CD16A (FcγRIIIa) 158F — the risk was reduced by 32%.
Among all the participants, the objective response rate — the percentage of participants whose tumors got smaller after treatment — was 22% for Margenza and 16% for Herceptin.
A final analysis on overall survival in the trial is expected next year.
Common adverse events associated with Margenza were fatigue (57%), nausea (33%), diarrhea (25%), and vomiting (21%). The therapy can also cause infusion-related reactions, which occurred in 13% of Margenza-treated patients, and most were relatively mild in severity.
The newly approved therapy has a boxed warning for left ventricular dysfunction (a heart condition) and for embryo-fetal toxicity, meaning that the therapy can cause toxic effects on a developing fetus.
MacroGenics, in collaboration with Zai Lab, is further testing Margenza in people with advanced HER2-positive gastroesophageal cancer — HER2 is also implicated in the growth of some of these tumors — in the ongoing global MAHOGONY trial (NCT04082364).
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