margenza

New breast cancer drug: MARGENZA (margetuximab-cmkb) is the first Her2-targeted treatment. Combined with Herceptin (trastuzumab) and chemotherapy, it can improve progression-free survival (PFS).

Recently, the U.S. Food and Drug Administration (FDA) has approved MARGENZA (margetuximab-cmkb) 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 is for metastatic disease.

MARGENZA (margetuximab-cmkb) is an Fc-engineered monoclonal antibody targeting the HER2 oncoprotein. HER2 is expressed by tumor cells in breast cancer, gastroesophageal cancer, and other solid tumors. Similar to trastuzumab, margetuximab-cmkb inhibits tumor cell proliferation, reduces HER2 extracellular domain shedding and mediates antibody-dependent cellular cytotoxicity (ADCC).

Approval date: December 16, 2020 Company: MacroGenics, Inc

MARGENZA (margetuximab-cmkb) Injection, for Intravenous Use

Initial U.S. Approval: 2020

Warnings: Left ventricular dysfunction and endosperm toxicity, see full prescribing information for complete boxed warnings.

Left ventricular dysfunction: MARGENZA may cause a decrease in left ventricular ejection fraction (LVEF). Assess cardiac function before and during treatment, and discontinuation of MARGENZA therapy may confirm a clinically significant decrease in left ventricular function.

Embryo-fetal toxicity: Exposure to MARGENZA during pregnancy may cause embryo-fetal harm. Inform patients of the risks and the need for effective contraception.

Mechanism of action

Margetuximab-cmkb binds to the extracellular domain of human epidermal growth factor receptor 2 protein (HER2). Upon binding to HER2-expressing tumor cells, margetuximab-cmkbin inhibits tumor cell proliferation, reduces shedding of the HER2 extracellular domain and mediates antibody-dependent cellular cytotoxicity (ADCC).

In vitro, the Fc region modified by margetuximab-cmkb increased binding to the activating Fcreceptor FCGR3A (CD16A) and reduced binding to the inhibitory Fc receptor FCGR2B (CD32B). These changes resulted in greater activation of ADCC and NK cells in vitro.

Indications and Uses

MARGENZA is a HER2/neu receptor antagonist indicated for use 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 therapies, at least one of which targeted metastatic disease.

Dosage and Administration

For intravenous infusion only.

Administer MARGENZA as an intravenous infusion of 15 mg/kg over 120 minutes for the initial dose, then all subsequent doses at least 30 minutes apart every 3 weeks.

On days when MARGENZA and chemotherapy are used at the same time, MARGENZA can be used immediately after chemotherapy is completed.

Dosage Form and Strength

Injection: 250mg/10mL (25mg/mL) in single-dose vial

Contraindications

• None.

Warnings and Precautions

•Infusion-Related Reaction (IRR): Monitor for signs and symptoms, slow or interrupt the infusion and institute appropriate medical therapy if a significant infusion-related reaction occurs.

Adverse Reactions

The most common adverse drug reactions (>10%) of MARGENZA in combination with chemotherapy are fatigue/asthenia, nausea, diarrhea, vomiting, constipation, headache, pyrexia, alopecia, abdominal pain, peripheral neuropathy, arthralgia/myalgia, cough, decreased appetite, dyspnea, infusion-related reactions, palmar-erythema paresthesia, and extremity pain.