Head-to-head data
See results from the pivotal SOPHIA trial
View study resultsMechanism of Action (MOA)
For illustration only.
MARGENZA is the first and only FDA-approved, Fc‑engineered, HER2-targeted monoclonal antibody (mAb) designed to optimize immune activation1,2*
*Based on in vitro data. The clinical relevance of in vitro data is unknown. Therefore, no conclusions can be drawn.
Watch this video to see how the engineered Fc region of MARGENZA works
MARGENZA has 2 functional regions: the Fab region and the engineered Fc region1,3
The anti-HER2 Fab region of the antibody binds to the HER2 receptor on tumor cells, inhibiting tumor cell proliferation.1,3
The engineered Fc region of MARGENZA binds to Fcγ receptors on innate immune effector cells such as natural killer (NK) cells. This binding activity recruits immune cells to the tumor site and mediates antibody-dependent cellular cytotoxicity (ADCC), resulting in apoptosis and tumor cell death.1,3-5*
*Based on in vitro data. The clinical relevance of in vitro data is unknown. Therefore, no conclusions can be drawn.
The engineered Fc region increases immune activity in vitro1
The Fcγ region of MARGENZA is purposely distinct in that it has 5 amino acid substitutions designed to increase binding affinity to the activating Fcγ receptor FcγRIIIA (CD16A) on NK cells, supporting ADCC in vitro.1,4,6 In addition, the engineered Fc region of MARGENZA decreases binding to inhibitory Fcγ receptor FcγRIIB (CD32B) present on immune effector cells, such as macrophages.1,3,4
Fab=fragment antigen-binding; Fc=fragment crystallizable; Fcγ=Fc gamma; HER2=human epidermal growth factor receptor 2.
Safety
Explore the safety profile of MARGENZA
See safetyDosing and administration
See how to properly administer MARGENZA
Dosing informationReferences: 1. MARGENZA® (margetuximab-cmkb). Prescribing Information. TerSera Therapeutics LLC. 2. Musolino A, Gradishar WJ, Rugo HS, et al. Role of Fcγ receptors in HER2-targeted breast cancer therapy. J Immunother Cancer. 2022;10(1):e003171. doi:10.1136/jitc-2021-003171 3. Zahavi D, AlDeghaither D, O'Connell A, Weiner LM. Enhancing antibody-dependent cell-mediated cytotoxicity: a strategy for improving antibody-based immunotherapy. Antib Ther. 2018;1(1):7-12. 4. Nordstrom JL, Gorlatov S, Zhang W, et al. Anti-tumor activity and toxicokinetics analysis of MGAH22, an anti-HER2 monoclonal antibody with enhanced Fcγ receptor binding properties. Breast Cancer Res. 2011;13(6):R123. doi:10.1186/bcr3069 5. Bang YJ, Giaccone G, Im SA, et al. First-in-human phase 1 study of margetuximab (MGAH22), an Fc-modified chimeric monoclonal antibody, in patients with HER2-positive advanced solid tumors. Ann Oncol. 2017;28(4):855-861. doi:10.1093/annonc/mdx002 6. Rugo HS, Im SA, Cardoso F, et al. Efficacy of margetuximab vs trastuzumab in patients with pretreated ERBB2-positive advanced breast cancer: a phase 3 randomized clinical trial. JAMA Oncol. 2021;7(4):573-584. doi:10.1001/jamaoncol.2020.7932
Indication
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.
Important Safety Information
BOXED WARNING: LEFT VENTRICULAR DYSFUNCTION AND EMBRYO-FETAL TOXICITY
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Left Ventricular Dysfunction: MARGENZA may lead to reductions in left ventricular ejection fraction (LVEF). Evaluate cardiac function prior to and during treatment. Discontinue MARGENZA treatment for a confirmed clinically significant decrease in left ventricular function.
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Embryo-Fetal Toxicity: Exposure to MARGENZA during pregnancy can cause embryo-fetal harm. Advise patients of the risk and need for effective contraception.
Additional Important Safety Information
Left Ventricular Dysfunction
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Evaluate cardiac function within 4 weeks prior to and every 3 months during and upon completion of treatment.
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In the pivotal SOPHIA trial, left ventricular dysfunction occurred in 1.9% of patients treated with MARGENZA.
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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.
Embryo-Fetal Toxicity
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Based on findings in animals and mechanism of action, MARGENZA can cause fetal harm when administered to a pregnant woman.
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Verify pregnancy status of women of reproductive potential prior to initiation of MARGENZA.
Infusion-Related Reactions (IRRs)
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MARGENZA can cause IRRs. Monitor patients during and after MARGENZA infusion for signs and symptoms. If a significant infusion-associated reaction occurs, slow or interrupt the infusion and administer appropriate medical therapies.
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In the pivotal SOPHIA trial, IRRs were reported by 13% of patients on MARGENZA plus chemotherapy. Most of the IRRs occur during Cycle 1. Grade 3 IRRs were reported in 1.5% of MARGENZA-treated patients.
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Interrupt MARGENZA infusion in patients experiencing dyspnea or clinically significant hypotension. Monitor patients until symptoms completely resolve.
Most Common Adverse Reactions
The most common adverse drug reactions (>10%) with MARGENZA in combination with chemotherapy in order of frequency 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.
To report SUSPECTED ADVERSE REACTIONS, contact the FDA at 1‑800‑FDA‑1088 or www.FDA.gov/medwatch. You may also contact TerSera Therapeutics at 1‑844‑334‑4035 or medicalinformation@tersera.com.
Please see accompanying Full Prescribing Information, including Boxed Warning.