Margetuximab-cmkb (Margenza®) received U.S. Food and Drug Administration approval in December 2020 for previously treated adults with metastatic HER2-positive breast cancer after clinical trials demonstrated increased progression-free and overall survival.
Immunotherapy, monoclonal antibody
Mechanism of Action
Margetuximab-cmkb inhibits the growth of tumor cells by binding to the HER2 protein’s extracellular domain. The drug also recruits natural killer cells and macrophages to mediate tumor cells’ antibody-dependent cellular cytotoxicity.
Used with chemotherapy to treat metastatic HER2-positive breast cancer in patients who have received two or more prior regimens targeting HER2, with one used for metastatic disease
15 mg/kg given as an IV infusion every three weeks (21-day cycle) until patients experience disease progression or unacceptable toxicity
Give by IV infusion over 120 minutes for the first dose; infuse subsequent doses over at least 30 minutes. If given concurrently with chemotherapy, administer margetuximab-cmkb immediately after the chemotherapy infusion is complete.
Margetuximab-cmkb includes two black box warnings for left ventricular dysfunction and embryo-fetal toxicity. Infusion-related reactions are also possible. When given in combination with chemotherapy, the most common side effects in more than 20% of patients include fatigue or asthenia, nausea, vomiting, and diarrhea. Laboratory findings include myelosuppression and increased activated partial thromboplastin time (aPTT), international normalized ratio, creatinine, alanine transaminase (ALT), aspartate aminotransferase (AST), lipase, and alkaline phosphatase.
Monitor patients for infusion-related reactions. Slow or interrupt the infusion and administer appropriate treatment if a significant reaction occurs. Consider premedications for patients who experience a mild or moderate infusion-related reaction.
Infuse medication through an IV line with a nonpyrogenic, low–protein-binding polyethersulfone (PES) 0.2 micron inline or add-on filter. Do not infuse other medications through the same line.
Avoid anthracyclines within four months after stopping margetuximab-cmkb because of the risk of cardiotoxicity. Because it may cause fetal harm if administered to pregnant individuals, conduct pregnancy testing prior to administration and advise patients of reproductive potential about the risk.
Teach patients to contact the healthcare team with signs of cardiac dysfunction, including shortness of breath; cough; palpitations; dizziness; swelling in the face, ankles, or legs; or sudden weight gain. Advise patients of reproductive potential about the risk for embryo-fetal toxicity and to use effective contraception for four months after receiving margetuximab-cmkb.
Follow safe handling precautions. Margetuximab-cmkb is potentially hazardous per the National Institute for Occupational Safety and Health definition (as described in U.S. Pharmacopeia General Chapter <800>) because of the risk for embryo-fetal toxicity.