margetuximab

Action and Spectrum

Actions and spectrum: 

margetuximab is a monoclonal antibody that targets human epidermal growth factor receptor 2 (HER2). It has been engineered to have increased binding affinity and enhanced immune effector function compared to the earlier generation of HER2-targeting antibodies. 

Breast and gastric cancers both have an overexpression of the transmembrane tyrosine kinase receptor HER2. By targeting HER2, margetuximab inhibits HER2-mediated signaling pathways that drive cancer cell proliferation, survival, and metastasis.

margetuximab also triggers immune-mediated mechanisms, such as antibody-dependent cellular cytotoxicity (ADCC), to induce the killing of HER2-overexpressing cancer cells by immune cells, such as natural killer cells and macrophages. 

margetuximab is indicated for treating metastatic HER2-positive breast cancer who have undergone two or more prior anti-HER2 regimens, at least one for metastatic disease. 

Drug Interaction

Adverse Reaction

Frequency defined 

>10% 

All Grades 

• Extremity pain (11%) 
• Palmoplantar erythrodysesthesia (13%) 
• Infusion-related reaction (13%) 
• Dyspnea (13%) 
• Cough (14%) 
• myalgia/ Arthralgia (14%) 
• Decreased appetite (14%) 
• Peripheral neuropathy (16%) 
• Abdominal pain (17%) 
• Alopecia (18%) 
• Pyrexia (19%) 
• Headache (19%) 
• Constipation (19%) 
• Alkaline phosphatase (21%) 
• Vomiting (21%) 
• Increased AST (23%) 
• Increased INR (24%) 
• Diarrhea (25%) 
• Increased lipase (30%) 
• Decreased lymphocytes (31%) 
• Increased ALT (32%) 
• Nausea (33%) 
• Decreased neutrophils (34%) 
• Decreased leukocytes (40%) 
• Decreased hemoglobin (52%) 
• asthenia/ Fatigue (57%) 
• Increased creatinine (68%) 

1-10% 

All Grades 

• Syncope (1.5%) 
• Hypertension (5%) 
• Decreased weight (6%) 
• Rash (6%) 
• Dysgeusia (6%) 
• Insomnia (6%) 
• Stomatitis (10%) 
• Dizziness (10%) 

Grade 3 or 4 

• Nausea (1.1%) 
• Dyspnea (1.1%) 
• Peripheral neuropathy (1.1%) 
• Increased INR (1.2%) 
• Infusion-related reaction (1.5%) 
• Abdominal pain (1.5%) 
• Increased ALT (2%) 
• Increased AST (2%) 
• Diarrhea (2.3%) 
• Decreased hemoglobin (3.2%) 
• Increased aPTT (3.4%) 
• Decreased lymphocytes (4.4%) 
• Decreased leukocytes (5%) 
• Increased lipase (6%) 
• Fatigue (7%) 
• Decreased neutrophils (9%) 

<1% 

Grade 3 or 4 

• Pyrexia (0.4%) 
• Decreased appetite (0.4%) 
• Increased creatinine (0.4%) 
• Cough (0.4%) 
• Arthralgia/myalgia (0.4%) 
• Vomiting (0.8%) 
• Extremity pain (0.8%) 
• Constipation (0.8%) 

Black Box Warning

Contraindication / Caution

Contraindication/Caution: 

Contraindication: 

margetuximab is contraindicated in patients with a history of severe infusion-related reactions to the medication or to other monoclonal antibodies. It should not be used during pregnancy unless clearly needed, as it may cause fetal harm. margetuximab is also contraindicated in patients with a history of hypersensitivity reactions to the active substance.  

Caution: 

• Infusion-related reactions: margetuximab can cause infusion-related reactions, including fever, chills, rigors, dyspnea, bronchospasm, and hypotension. These reactions typically occur during or within 24 hours of the infusion. Patients should be monitored closely for any signs or symptoms of infusion-related reactions, and appropriate medical management should be provided as necessary. 
• Cardiotoxicity: margetuximab has been associated with an increased risk of cardiotoxicity, including left ventricular dysfunction and heart failure. Patients with pre-existing cardiac disease or risk factors for cardiotoxicity should be closely monitored during treatment with margetuximab. 
• Embryo-fetal toxicity: margetuximab may cause fetal harm when administered to pregnant women. Women of childbearing should be advised to use effective contraception during treatment with margetuximab and for at least four months after the last dose. 
• Interference with HER2 testing: margetuximab can interfere with HER2 testing, potentially leading to false-positive or false-negative results. Patients who have previously been tested for HER2 status should be retested using an appropriate assay prior to starting treatment with margetuximab. 
• Immunogenicity: As with all therapeutic proteins, there is a potential for immunogenicity with margetuximab. Patients should be monitored for any signs or symptoms of immune-mediated adverse reactions, and appropriate medical management should be provided as necessary.

Comorbidities: 

margetuximab is a monoclonal antibody used in the treatment of certain types of cancer. There are no specific comorbidities associated with the use of margetuximab.

However, patients with cancer may have other comorbidities that determine the appropriate treatment plan, including but not limited to cardiovascular disease, respiratory disease, and renal impairment.

The use of margetuximab may need to be adjusted or avoided in patients with certain comorbidities or in those who are taking medications that may interact with it, as with any medication. 

Pregnancy / Lactation

Pregnancy consideration: pregnancy category C 

Lactation: safety and efficacy not established  

Pregnancy category: 

• Category A: Satisfactory and well-controlled studies show no risk to the fetus in the first or later trimester. 
• Category B: There is no evidence of risk to the fetus found in animal reproduction studies and there are not enough studies on pregnant women. 
• Category C: Adverse effects on the fetus found with evidence in animal reproduction studies and no adequate evidence for an effect in humans, care must be taken for potential risks in pregnant women. 
• Category D: There is adequate data available with sufficient evidence of human fetal risk from various platforms, but despite potential risks may be used only in emergency cases for potential benefits. 
• Category X: Drugs listed in this category outweigh risks over benefits These category drugs should be prohibited for pregnant women. 
• Category N: There is no data available for the drug under this category. 

Pharmacology

Pharmacology: 

margetuximab is a monoclonal antibody that targets the human epidermal growth factor receptor 2 (HER2). It works by binding to the HER2 receptor and inhibiting its downstream signaling pathways, which leads to the inhibition of tumor cell growth and survival.

margetuximab also mediates antibody-dependent cell-mediated cytotoxicity (ADCC), which involves immune cells, such as natural killer cells, macrophages, and neutrophils, that can recognize and destroy HER2-overexpressing cancer cells. 

margetuximab has a half-life of approximately 12.4 days, and it is primarily eliminated through catabolism and proteolysis. It does not induce or inhibit CYP450 enzymes, nor does it undergo renal excretion.  

Pharmacodynamics: 

margetuximab is a monoclonal antibody that targets the human epidermal growth factor receptor 2 (HER2). Breast and gastric cancers both have an overexpression of the transmembrane tyrosine kinase receptor HER2.

margetuximab binds to the extracellular domain of HER2, leading to the inhibition of HER2-mediated signaling pathways and inducing antibody-dependent cellular cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC) against HER2-expressing cells. 

In preclinical studies, margetuximab has demonstrated enhanced ADCC and CDC activity compared to trastuzumab, another monoclonal antibody targeting HER2. margetuximab has also been shown to inhibit the formation of HER2 homodimers and heterodimers with other members of the HER family, leading to decreased HER2-mediated signaling and cell proliferation.  

Pharmacokinetics: 

Absorption 

margetuximab is administered via intravenous infusion and is rapidly and completely absorbed into the systemic circulation. 

Distribution 

The volume of distribution of margetuximab is approximately 6.2 L. It binds to the human epidermal growth factor receptor 2 (HER2) on the cell surface. 

Metabolism 

margetuximab is not metabolized by the liver, and it does not induce or inhibit cytochrome P450 enzymes. 

Elimination and excretion 

The elimination half-life of margetuximab is approximately 14.7 days. It is primarily eliminated via the reticuloendothelial system. The primary route of excretion for margetuximab is through the reticuloendothelial system. 

Adminstartion

Administration: 

margetuximab is administered as an intravenous (IV) infusion by a healthcare professional. The infusion is typically given over a period of 120 minutes, although the exact duration may vary depending on the patient’s condition and individual needs.

The recommended dose of margetuximab may also vary depending on the patient’s weight and other factors. Patients should be monitored closely for any signs of an allergic reaction or other adverse effects during and after the infusion. 

Patient Information Leaflet

Patient information leaflet 

Generic Name: margetuximab 

Pronounced: [ MAR-je-TUX-i-mab ]  

Why do we use margetuximab? 

margetuximab is a monoclonal antibody used for the treatment of metastatic HER2-positive breast cancer in patients who have taken at least two prior anti-HER2 regimens, including trastuzumab and pertuzumab.

It is used in combination with chemotherapy, specifically, the chemotherapy drug capecitabine. margetuximab works by binding to HER2 receptors on the surface of cancer cells, leading to antibody-dependent cellular cytotoxicity and the destruction of the cancer cells.