Margetuximab — Drug Monograph

Brand names: Margenza

Drug class: Monoclonal Antibody

Mechanism of Action

Margetuximab is an Fc-engineered, HER2-targeted monoclonal antibody. While its Fab domain binds to the same epitope of HER2 as trastuzumab, its Fc domain has been modified with five amino acid substitutions to increase affinity for the activating receptor CD16A (FcγRIIIa) and decrease affinity for the inhibitory receptor CD32B (FcγRIIb). This engineering enhances the activation of Natural Killer (NK) cells and macrophages, leading to increased antibody-dependent cellular cytotoxicity (ADCC) against HER2-expressing tumor cells. It effectively bypasses some of the limitations of trastuzumab in…

FDA Indications

• 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.

Common Side Effects

• Fatigue
• Nausea
• Diarrhea
• Vomiting
• Constipation
• Headache
• Pyrexia
• Alopecia
• Abdominal pain
• Peripheral neuropathy

Clinical Pearl

Margetuximab is essentially "optimized trastuzumab." Its primary advantage is seen in patients who carry the CD16A 158F allele (low affinity), which is present in about 85% of the population. In the SOPHIA trial, this subgroup showed a more pronounced progression-free survival benefit compared to those receiving trastuzumab, highlighting the clinical value of Fc-engineering to overcome genetic variations in immune response.

Related Therapies & Mechanisms

• Pertuzumab (Perjeta) — Monoclonal Antibody · Breast
• Trastuzumab (Herceptin) — Monoclonal Antibody · Breast
• Alemtuzumab (Campath) — Monoclonal Antibody
• Amivantamab (Rybrevant) — Monoclonal Antibody