MARGENZA
Clinical safety rating
cautionComprehensive clinical and safety monograph for MARGENZA (MARGENZA).
Comprehensive clinical and safety monograph for MARGENZA (MARGENZA).
FDA-approved: In combination with chemotherapy (capecitabine or gemcitabine plus cisplatin) for the treatment of adults with metastatic or locally advanced unresectable HER2-positive gastric or gastroesophageal junction adenocarcinoma who have received two or more prior anti-HER2 regimens.Off-label: Not specified in FDA labeling; potential off-label uses may include other HER2-positive malignancies, but none are established.
Margetuximab is an Fc-engineered monoclonal antibody that targets the extracellular domain of human epidermal growth factor receptor 2 (HER2). It binds to HER2 on tumor cells and mediates antibody-dependent cellular cytotoxicity (ADCC) via enhanced affinity for activating Fcγ receptors (FcγRIIIa) and reduced affinity for inhibitory FcγRIIb, thereby augmenting immune effector cell activation.
| Metabolism | Margetuximab is a monoclonal antibody; it is degraded into small peptides and amino acids via general protein catabolism. No specific metabolic enzymes or pathways are involved. |
| Excretion | Primarily cleared via proteolytic degradation; renal excretion of intact drug is negligible (<1%). No significant biliary or fecal elimination reported. |
| Half-life | Terminal half-life approximately 17-23 days (mean ~20 days) following intravenous administration, supporting a 3-week dosing interval for sustained receptor occupancy. |
| Protein binding | ~99% bound to plasma proteins, primarily to albumin and immunoglobulin G (as a monoclonal antibody). |
| Volume of Distribution | Volume of distribution approximately 3.0-4.0 L (0.04-0.06 L/kg). Low Vd indicates limited extravascular distribution, consistent with large antibody molecule primarily confined to plasma and interstitial space. |
| Bioavailability | Bioavailability is 100% by intravenous route as it is administered as an IV infusion; not available for oral or other routes. |
| Onset of Action | Onset of clinical effect is typically observed within 2-4 weeks after first dose, based on radiographic response in clinical trials; maximum effect may require multiple cycles (~6-12 weeks). |
| Duration of Action | Duration of action extends throughout the dosing interval (3 weeks) with sustained HER2 receptor blockade; clinical effect persists for several weeks after treatment cessation due to long half-life. |
| Molecular Weight | 149220 |
15 mg/kg intravenously over 60 minutes every 3 weeks until disease progression or unacceptable toxicity.
| Dosage form | INJECTABLE |
| Renal impairment | No dose adjustment recommended for mild to moderate renal impairment (CrCl ≥30 mL/min). Not studied in severe renal impairment (CrCl <30 mL/min) or end-stage renal disease. |
| Liver impairment | No dose adjustment recommended for mild hepatic impairment (total bilirubin ≤ ULN and AST > ULN, or total bilirubin >1-1.5× ULN with any AST). Not studied in moderate (total bilirubin >1.5-3× ULN with any AST) or severe (total bilirubin >3× ULN with any AST) hepatic impairment. |
| Pediatric use | Safety and effectiveness in pediatric patients have not been established. |
| Geriatric use | No specific dose adjustment recommended. Of the 292 patients treated with MARGENZA in the SOPHIA trial, 45% were aged 65 years or older, 11% were 75 or older. No overall differences in efficacy or safety observed between elderly and younger patients. |
| 1st trimester | MARGENZA (margetuximab-cmkb) is an IgG1 monoclonal antibody. IgG molecules are known to cross the placenta in increasing amounts as pregnancy progresses, with the greatest transfer occurring in the third trimester. For the first trimester, placental transfer is minimal; however, there is limited human data. Based on its mechanism of action (HER2/neu receptor blockade), there is potential for fetal harm, including oligohydramnios and fetal renal impairment. Use is not recommended unless clearly needed. |
| 2nd trimester | During the second trimester, placental transfer of IgG increases. There is a risk of fetal toxicities similar to other HER2-directed antibodies, including fetal growth restriction and oligohydramnios. Use is contraindicated unless potential benefit outweighs risk. |
| 3rd trimester | In the third trimester, IgG transfer is maximal. Exposure is associated with significant risk of oligohydramnios, fetal anuria, and neonatal renal failure. Use is contraindicated in the third trimester. |
Clinical note
Comprehensive clinical and safety monograph for MARGENZA (MARGENZA).
| Placental transfer | Margetuximab is a humanized IgG1 monoclonal antibody; IgG is known to cross the placental barrier by FcRn-mediated transport. Transfer increases as pregnancy progresses, reaching the highest levels in the third trimester. Human data are lacking but animal studies suggest fetal transfer. |
| Breastfeeding | It is unknown whether margetuximab is excreted in human milk. However, human IgG is present in colostrum and breast milk. Because of the potential for adverse reactions in the nursing infant, including immune suppression and gastrointestinal disturbances, breastfeeding is not recommended during treatment and for at least 5 months after the last dose. |
| Lactation Rating | L5 (Contraindicated) |
| Teratogenic Risk | MARGENZA (margetuximab-cmkb) is an IgG1 monoclonal antibody. Based on its mechanism of action (HER2/neu receptor blockade) and findings from animal studies with other HER2-targeted agents, it is expected to cause fetal harm or death when administered to a pregnant woman. Human IgG molecules cross the placenta, with increasing transfer as pregnancy progresses, reaching peak levels during the third trimester. There are no adequate and well-controlled studies in pregnant women. First trimester exposure may have lower risk, but second and third trimester exposure is associated with oligohydramnios, fetal renal dysfunction, and fetal loss. |
| Fetal Monitoring | Monitor pregnancy status in women of reproductive potential. If MARGENZA is used during pregnancy or if the patient becomes pregnant while receiving the drug, apprise the patient of the potential hazard to the fetus. Perform serial ultrasound examinations to assess for oligohydramnios and fetal renal function if exposure occurs during the second or third trimester. Consider pregnancy testing prior to initiation in women of childbearing potential. |
| Fertility Effects | MARGENZA may impair fertility in females based on findings from animal studies with anti-HER2 antibodies, which have shown effects on female reproductive organs, including ovarian failure and decreased fertility. No data are available on male fertility. The potential for fertility impairment in humans is unknown. |
■ FDA Black Box Warning
No black box warning exists for MARGENZA.
| Serious Effects |
None known based on prescribing information. However, use during pregnancy is not recommended.
| Precautions | Cardiotoxicity: Left ventricular ejection fraction (LVEF) decline; assess LVEF prior to and during treatment. Discontinue for symptomatic heart failure or persistent decline., Infusion-related reactions: Monitor during infusion; reduce rate or discontinue for severe reactions., Embryo-fetal toxicity: Can cause fetal harm; advise females of reproductive potential of the risk and use effective contraception., Pulmonary toxicity: Interstitial lung disease and pneumonitis; monitor for signs/symptoms and permanently discontinue if confirmed., Neutropenia and febrile neutropenia: May occur; monitor blood counts., Hypokalemia and hypomagnesemia: Monitor electrolytes and replace as needed. |
| Food/Dietary | No specific food interactions are known. No dietary restrictions required during treatment. |
| Clinical Pearls | MARGENZA (margetuximab-cmkb) is an anti-HER2 monoclonal antibody indicated in combination with chemotherapy for metastatic HER2-positive breast cancer after two or more prior anti-HER2 regimens. Premedicate with acetaminophen, diphenhydramine, and corticosteroids to mitigate infusion-related reactions. Monitor for left ventricular ejection fraction (LVEF) decline; assess cardiac function at baseline and every 3 months during treatment. Use with caution in patients with prior anthracycline exposure or pre-existing cardiac dysfunction. |
| Patient Advice | MARGENZA is given as an intravenous infusion every 3 weeks; each infusion takes about 90 minutes initially, then 30 minutes if well tolerated. · You may experience infusion-related reactions such as fever, chills, or nausea; you will receive premedication to reduce these. · This drug can cause heart problems; your doctor will monitor your heart function with echocardiograms regularly. · MARGENZA can cause fetal harm if used during pregnancy; use effective contraception during treatment and for 4 months after the last dose. · Do not breastfeed during treatment and for 4 months after the last dose. · Common side effects include fatigue, nausea, diarrhea, and anemia. |
Loading safety data…