{"entity":{"id":"margetuximab","kind":"drug","name":"Margetuximab","aka":[],"tldr":"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.","status":"approved","asOf":"2026-09-07","wikipedia":"https://en.wikipedia.org/wiki/Margetuximab","links":[{"label":"FDA label (DailyMed)","url":"https://dailymed.nlm.nih.gov/dailymed/search.cfm?query=Margetuximab"}],"tags":[],"related":[],"cancers":["breast-her2-positive"],"sections":[],"technologies":["monoclonal-antibody"],"targets":["her2"],"drugs":[],"companies":["macrogenics"],"institutions":[],"pathways":[],"terms":["adcc","fc-effector"],"trials":["nct02492711","nct04082364","nct04425018"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"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":[{"region":"US","year":2020,"indication":"HER2+ metastatic breast cancer after ≥2 anti-HER2 regimens, with chemotherapy"}],"mechanismSteps":[],"dosing":{"route":"Intravenous","schedule":"15 mg/kg every 3 weeks with chemotherapy"},"toxicity":[{"event":"Infusion-related reactions","anyGradePct":13},{"event":"Left ventricular dysfunction","anyGradePct":2}],"access":[],"regulatoryEvents":[]},"route":"/drugs/margetuximab/","neighbours":{"cancer":[{"id":"breast-her2-positive","kind":"cancer","name":"HER2-positive breast cancer","route":"/cancers/breast-her2-positive/"}],"technology":[{"id":"monoclonal-antibody","kind":"technology","name":"Monoclonal antibodies","route":"/technologies/monoclonal-antibody/"}],"target":[{"id":"her2","kind":"target","name":"HER2","route":"/targets/her2/"}],"company":[{"id":"macrogenics","kind":"company","name":"MacroGenics","route":"/companies/macrogenics/"}],"term":[{"id":"adcc","kind":"term","name":"ADCC (antibody-dependent cellular cytotoxicity)","route":"/terms/adcc/"},{"id":"fc-effector","kind":"term","name":"Fc engineering / effector function","route":"/terms/fc-effector/"}],"trial":[{"id":"nct04082364","kind":"trial","name":"Combination Margetuximab, Retifanlimab, Tebotelimab, and Chemotherapy Phase 2/3 Trial in HER2+ Gastric/GEJ Cancer","route":"/trials/nct04082364/"},{"id":"nct04425018","kind":"trial","name":"MARGetuximab Or Trastuzumab (MARGOT)","route":"/trials/nct04425018/"},{"id":"nct02492711","kind":"trial","name":"Margetuximab Plus Chemotherapy vs Trastuzumab Plus Chemotherapy in the Treatment of HER2+ Metastatic Breast Cancer","route":"/trials/nct02492711/"}],"pathway":[{"id":"nk-cell-recognition","kind":"pathway","name":"NK-cell recognition: missing self & stress ligands","route":"/pathways/nk-cell-recognition/"}],"biomarker":[{"id":"her2-ihc-3-plus","kind":"biomarker","name":"HER2 IHC 3+ (HER2-positive by immunohistochemistry)","route":"/biomarkers/her2-ihc-3-plus/"}]}}