Margetuximab

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

• MARGENZA is indicated, 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 [see Dosage and Administration (2.1) and Clinical Studies (14.1) ]. MARGENZA is a HER2/neu receptor antagonist indicated, 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.ICD-10: C50.919

• None. None.contraindicated

For intravenous infusion only. ( 2.1 ) Administer MARGENZA as an intravenous infusion at 15 mg/kg over 120 minutes for the initial dose, then over a minimum of 30 minutes every 3 weeks for all subsequent doses. ( 2.1 ) On days when both MARGENZA and chemotherapy are to be administered, MARGENZA may be administered immediately after chemotherapy completion. ( 2.1 ) 2.1 Recommended Doses and Schedules The recommended dose of MARGENZA is 15 mg/kg, administered as an intravenous infusion every 3 weeks (21-day cycle) until disease progression or unacceptable toxicity. Administer MARGENZA as an intravenous infusion at 15 mg/kg over 120 minutes for the initial dose, then over a minimum of 30 minutes every 3 weeks for all subsequent doses. On days when both MARGENZA and chemotherapy are to be administered, MARGENZA may be administered immediately after chemotherapy completion. Refer to the respective Prescribing Information for each therapeutic agent administered in combination with MARGENZA for the recommended dosage information, as appropriate. 2.2 Dose Modification or Important Dosing Considerations If a patient misses a dose of MARGENZA, administer the scheduled dose as soon as possible. Adjust the administration schedule to maintain a 3-week interval between doses. Left Ventricular Dysfunction [see Warnings and Precautions (5.1) ] Assess left ventricular ejection fraction (LVEF) before starting MARGENZA and regularly during treatment.

Infusion-Related Reactions (IRRs): Monitor for signs and symptoms. If a significant infusion-associated reaction occurs, slow or interrupt the infusion and administer appropriate medical therapies. ( 5.3 ) 5.1 Left Ventricular Dysfunction Left ventricular cardiac dysfunction can occur with MARGENZA. In SOPHIA, left ventricular dysfunction occurred in 1.9% of patients treated with MARGENZA. MARGENZA has not been studied in patients with a pretreatment LVEF value of < 50%, a prior history of myocardial infarction or unstable angina within 6 months, or congestive heart failure NYHA class II-IV. Withhold MARGENZA for ≥ 16% absolute decrease in LVEF from pretreatment values or LVEF value below institutional limits of normal (or 50% if no limits are available) and ≥ 10% absolute decrease in LVEF from pretreatment values. Permanently discontinue MARGENZA if LVEF decline persists for greater than 8 weeks, or if dosing is interrupted on greater than 3 occasions due to LVEF decline [see Dosage and Administration (2.2) ]. Cardiac Monitoring Conduct thorough cardiac assessment, including history, physical examination, and determination of LVEF by echocardiogram or MUGA scan. The following schedule is recommended: Baseline LVEF measurement within 4 weeks prior to initiation of MARGENZA LVEF measurements (MUGA/echocardiogram) every 3 months during and upon completion of MARGENZA Repeat LVEF measurement at 4-week intervals if MARGENZA is withheld for significant left ventricular cardiac dysfunction [see Dosage and Administration (2.2) ] .

The following adverse reactions are discussed in greater detail in other sections of the label: Left Ventricular Dysfunction [see Warnings and Precautions (5.1) ] Embryo-Fetal Toxicity [see Warnings and Precautions (5.2) ] Infusion-Related Reactions [see Warnings and Precautions (5.3) ] The most common adverse drug reactions (>10%) with 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-plantar erythrodysesthesia, and extremity pain. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact TerSera Therapeutics LLC at 1-844-334-4035 or medicalinformation@tersera.com or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect rates observed in practice. The safety of MARGENZA was evaluated in HER2-positive breast cancer patients who received two or more prior anti-HER2 regimens in SOPHIA [see Clinical Studies (14.1) ]. Patients were randomized (1:1) to receive either MARGENZA 15 mg/kg every 3 weeks plus chemotherapy or trastuzumab plus chemotherapy. Among patients who received MARGENZA, 40% were exposed for 6 months or longer and 11% were exposed for greater than one year.

Females and Males of Reproductive Potential: Verify the pregnancy status of females prior to initiation of MARGENZA. ( 8.3 ) 8.1 Pregnancy Risk Summary Based on findings in animals and mechanism of action, MARGENZA can cause fetal harm when administered to a pregnant woman. There are no available data on use of MARGENZA in pregnant women to inform the drug-associated risk. In postmarketing reports, use of a HER2-directed antibody during pregnancy resulted in cases of oligohydramnios and oligohydramnios sequence manifesting as pulmonary hypoplasia, skeletal abnormalities, and neonatal death. In an animal reproduction study, intravenous administration of margetuximab-cmkb to pregnant cynomolgus monkeys once every 3 weeks, starting at gestational day (GD) 20 until delivery, resulted in oligohydramnios and delayed infant kidney development. Animal exposures were ≥ 3 times the human exposures at the recommended dose, based on C max (see Data ) . Advise patients of potential risks to a fetus. There are clinical considerations if MARGENZA is used during pregnancy or within 4 months prior to conception (see Clinical Considerations ). Estimated background risk of major birth defects and miscarriage for the indicated population is unknown. In the U.S.

Metabolism

Following the approved recommended dosage, the steady-state geometric mean (%CV) C max of margetuximab-cmkb is 466 (20%) µg/mL and AUC 0-21d is 4120 (21%) µg.day/mL in patients with HER2-positive relapsed or refractory advanced breast cancer. Margetuximab-cmkb undergoes both linear and nonlinear elimination.

• Dec 16, 2020BLABLA761150Macrogenics Inc

1. 1Death519%
2. 2Disease Progression519%
3. 3Chills312%
4. 4Infusion Related Reaction27.7%
5. 5Abdominal Pain13.8%
6. 6Alopecia13.8%
7. 7Anaphylactic Reaction13.8%
8. 8Asthenia13.8%
9. 9Blood Pressure Decreased13.8%
10. 10Cardiac Disorder13.8%
11. 11Constipation13.8%
12. 12Diarrhoea13.8%
13. 13Drug Ineffective13.8%
14. 14Drug Intolerance13.8%
15. 15Fatigue13.8%

The 10 most recently updated of 12 ClinicalTrials.gov registrations naming Margetuximab as an intervention. Registration is not evidence of efficacy or safety — reference crosswalk only.

• Pilot Study of [68Ga]Ga-ABY-025 Imaging in Patients Undergoing Treatment With HER2-targeted Therapy
  Recruiting · Early phase 1 · Interventional · 30 enrolled · Vanderbilt-Ingram Cancer Center
  NCT06828588updated 2026-05-08
• MARGetuximab Or Trastuzumab (MARGOT)
  Active not recruiting · Phase 2 · Interventional · 174 enrolled · Dana-Farber Cancer Institute
  NCT04425018updated 2025-11-18
• Combination Margetuximab, Retifanlimab, Tebotelimab, and Chemotherapy Phase 2/3 Trial in HER2+ Gastric/GEJ Cancer
  Completed · Phase 2 · Phase 3 · Interventional · 82 enrolled · MacroGenics
  NCT04082364updated 2025-06-08
• Combination Margetuximab and Pembrolizumab for Advanced, Metastatic HER2(+) Gastric or Gastroesophageal Junction Cancer
  Completed · Phase 1 · Phase 2 · Interventional · 95 enrolled · MacroGenics
  NCT02689284updated 2025-03-17
• Margetuximab Plus Chemotherapy vs Trastuzumab Plus Chemotherapy in the Treatment of HER2+ Metastatic Breast Cancer
  Completed · Phase 3 · Interventional · 624 enrolled · MacroGenics
  NCT02492711updated 2025-03-17
• Phase 2 Study of the Monoclonal Antibody MGAH22 (Margetuximab) in Patients With Relapsed or Refractory Advanced Breast Cancer
  Completed · Phase 2 · Interventional · 25 enrolled · MacroGenics
  NCT01828021updated 2025-03-13
• Safety Study of MGAH22 in HER2-positive Carcinomas
  Completed · Phase 1 · Interventional · 66 enrolled · MacroGenics
  NCT01148849updated 2025-02-26
• Margetuximab Expanded Access Program
  Approved for marketing · Expanded access · TerSera Therapeutics LLC
  NCT03133988updated 2025-02-14
• A Study of MGD013 in Patients With Unresectable or Metastatic Neoplasms
  Completed · Phase 1 · Interventional · 277 enrolled · MacroGenics
  NCT03219268updated 2023-12-21
• A Study to Evaluate the Efficacy and Safety of Margetuximab Plus Chemotherapy in the Treatment of Chinese Patients With HER2+ MBC
  Unknown · Phase 2 · Interventional · 123 enrolled · Zai Lab (Shanghai) Co., Ltd.
  NCT04262804updated 2023-08-22

Frequently asked questions

How does Margetuximab work?

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

What is Margetuximab used for?

According to FDA labeling, Margetuximab carries indications including: MARGENZA is indicated, 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 [see Dosage and Administration (2.1) and Clinical Studies (14.1) ]. MARGENZA is a HER2/neu receptor antagonist indicated, 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.. This is a reference summary of labeled uses, not medical advice or a treatment recommendation.

What class of drug is Margetuximab?

Margetuximab is classified as HER2 (Human Epidermal Growth Factor Receptor 2) inhibitors, HER2/neu Receptor Antagonist, HER2/Neu/cerbB2 Antagonists, Cellular Proliferation Alteration.

What are the brand names for Margetuximab?

Margetuximab is marketed under brand names including Margenza.

What are the contraindications for Margetuximab?

Margetuximab labeling lists contraindications including: None. None.. Always consult the full prescribing information and a clinician.