# Margetuximab

Source: https://onco.cc/drugs/margetuximab/  
OnCo record `margetuximab` (Treatment). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

A trastuzumab look-alike with an engineered tail that binds immune cells more tightly; approved in 2020 but rarely used after ADCs arrived.

## Summary

Margetuximab is an anti-HER2 IgG1 antibody whose Fc region is engineered to bind the activating receptor FcγRIIIa (CD16A) more tightly and the inhibitory FcγRIIb less, enhancing antibody-dependent cellular cytotoxicity; its HER2-binding arm is otherwise trastuzumab-like. It is approved for HER2-positive metastatic breast cancer after two or more anti-HER2 regimens, given with chemotherapy at 15 mg/kg every 3 weeks. SOPHIA (versus trastuzumab, both with chemotherapy) showed PFS of 5.8 versus 4.9 months (HR 0.76); overall survival was not significantly improved, with a suggestion of benefit in CD16A-158F carriers. It was approved in December 2020 but is rarely used since antibody-drug conjugates arrived. It illustrates the ceiling of Fc engineering alone versus payload delivery. For a newcomer, it is a trastuzumab look-alike with a sharper immune tail that did not change practice.

## Fields

- Kind: Treatment
- Status: approved
- Last checked: 2026-09-07
- Brand: Margenza
- Modality: Fc-engineered monoclonal antibody (anti-HER2)
- Mechanism: Anti-HER2 IgG1 with Fc mutations increasing FcγRIIIa (CD16A) affinity and decreasing FcγRIIb binding, enhancing ADCC.
- Approvals: US 2020: HER2+ metastatic breast cancer after ≥2 anti-HER2 regimens, with chemotherapy
- Dosing: Intravenous; 15 mg/kg every 3 weeks with chemotherapy

## Sources

- Wikipedia: https://en.wikipedia.org/wiki/Margetuximab
- FDA label (DailyMed): https://dailymed.nlm.nih.gov/dailymed/search.cfm?query=Margetuximab

## Connected records

- cancers: [HER2-positive breast cancer](https://onco.cc/cancers/breast-her2-positive/)
- technologies: [Monoclonal antibodies](https://onco.cc/technologies/monoclonal-antibody/)
- targets: [HER2](https://onco.cc/targets/her2/)
- companies: [MacroGenics](https://onco.cc/companies/macrogenics/)
- terms: [ADCC (antibody-dependent cellular cytotoxicity)](https://onco.cc/terms/adcc/), [Fc engineering / effector function](https://onco.cc/terms/fc-effector/)
- trials: [Combination Margetuximab, Retifanlimab, Tebotelimab, and Chemotherapy Phase 2/3 Trial in HER2+ Gastric/GEJ Cancer](https://onco.cc/trials/nct04082364/), [MARGetuximab Or Trastuzumab (MARGOT)](https://onco.cc/trials/nct04425018/), [Margetuximab Plus Chemotherapy vs Trastuzumab Plus Chemotherapy in the Treatment of HER2+ Metastatic Breast Cancer](https://onco.cc/trials/nct02492711/)
- pathways: [NK-cell recognition: missing self & stress ligands](https://onco.cc/pathways/nk-cell-recognition/)
- biomarkers: [HER2 IHC 3+ (HER2-positive by immunohistochemistry)](https://onco.cc/biomarkers/her2-ihc-3-plus/)

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