Margetuximab

What it is and how it works

Mechanism of Action Margetuximab-cmkb binds to the extracellular domain of the human epidermal growth factor receptor 2 protein (HER2). Upon binding to HER2-expressing tumor cells, margetuximab-cmkb inhibits tumor cell proliferation, reduces shedding of the HER2 extracellular domain and mediates antibody-dependent cellular cytotoxicity (ADCC). In vitro, the modified Fc region of margetuximab-cmkb increases binding to activating Fc receptor FCGR3A (CD16A) and decreases binding to inhibitory Fc receptor FCGR2B (CD32B). These changes lead to greater in vitro ADCC and NK cell activation.

Mechanism class: HER2/Neu/cerbB2 Antagonists

Indications

is indicated, in combination with chemotherapy, for the treatment of adult patients with metastatic HER2-positive breast cancer who have received two or more prior anti-HER2 regimens, at least one of which was for metastatic disease . MARGENZA is a HER2/neu receptor antagonist indicated, in combination with chemotherapy, for the treatment of adult patients with metastatic HER2-positive breast cancer who have received two or more prior anti-HER2 regimens, at least one of which was for metastatic disease. ( 1 , 2.1 , 14.1 )

Dosage and administration (summary)

For intravenous infusion only. Administer MARGENZA as an intravenous infusion at 15 mg/kg over 120 minutes for the initial dose, then over a minimum of 30 minutes every 3 weeks for all subsequent doses. On days when both MARGENZA and chemotherapy are to be administered, MARGENZA may be administered immediately after chemotherapy completion. Recommended Doses and Schedules The recommended dose of MARGENZA is 15 mg/kg, administered as an intravenous infusion every 3 weeks (21-day cycle) until disease progression or unacceptable toxicity.

Contraindications

None. None.

Warnings and precautions

Infusion-Related Reactions (IRRs): Monitor for signs and symptoms. If a significant infusion-associated reaction occurs, slow or interrupt the infusion and administer appropriate medical therapies. Left Ventricular Dysfunction Left ventricular cardiac dysfunction can occur with MARGENZA. In SOPHIA, left ventricular dysfunction occurred in 1.9% of patients treated with MARGENZA. MARGENZA has not been studied in patients with a pretreatment LVEF value of < 50%, a prior history of myocardial infarction or unstable angina within 6 months, or congestive heart failure NYHA class II-IV.

Pregnancy

Pregnancy Risk Summary Based on findings in animals and mechanism of action, MARGENZA can cause fetal harm when administered to a pregnant woman. There are no available data on use of MARGENZA in pregnant women to inform the drug-associated risk.

Storage and supply

Storage Store vials refrigerated at 2°C to 8°C (36°F to 46°F) in original carton to protect from light until time of use. Do not freeze. Do not shake.

Source: Margetuximab-Cmkb (Margenza) — US FDA prescribing information, 2025-02-11, DailyMed. Summarised and shortened; the full label governs. Iranian registration, indications and labelling may differ.