A next generation monoclonal antibody (mAb)

MARGENZA (margetuximab-cmkb) is the first and only FDA-approved, Fc-engineered, HER2-targeted mAb designed to improve immune engagement.^1,2

MARGENZA was approved by the FDA in 2020 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.

Mechanism of action

See how the engineered Fc region of MARGENZA works.

MARGENZA is a mAb made up of 2 functional regions.^1,³

Microscopic image of MARGENZA antibody, labeling the anti-HER2 fragment antigen-binding (Fab) region and the Fc region — MARGENZA's molecule binding to the HER2 tumor cells.

The anti-HER2 fragment antigen-binding (Fab) region of the antibody binds to the HER2 receptor on tumor cells. This interaction is the source of MARGENZA’s antiproliferative activity.¹

The engineered fragment crystallizable (Fc) region of MARGENZA has been distinctly engineered in 5 locations.⁴ This mediates immune effects by recruiting the innate immune cells (natural killer [NK] cells and macrophages) in order to cause antibody-dependent cellular cytotoxicity (ADCC) of the tumor cells.^1,3

MARGENZA's molecule binding to the HER2 tumor cells.

The anti-HER2 fragment antigen-binding (Fab) region of the antibody binds to the HER2 receptor on tumor cells. This interaction is the source of MARGENZA’s antiproliferative activity.¹

The engineered Fc region increases immune activity in vitro compared with trastuzumab¹

The clinical relevance of in vitro data is unknown.

Microscopic shot of MARGENZA binding to the HER2 receptor — MARGENZA cell binding with the NK cell and tumor cell through Fcy and HER2 receptors.

Direct Anti-Tumor Activity¹

Inhibits tumor cell proliferation
Reduces shedding of HER2 extracellular domain

Fc Region Optimization¹

Increased binding to CD16A (activating)
Decreased binding to CD32B (inhibitory)

Antibody-Dependent Cellular Cytotoxicity (ADCC)^1,³

Immune cell-mediated anti-tumor activity
Greater in vitro ADCC and NK cell activation

MARGENZA cell binding with the NK cell and tumor cell through Fcy and HER2 receptors.

Direct Anti-Tumor Activity¹

Inhibits tumor cell proliferation
Reduces shedding of HER2 extracellular domain

Fc Region Optimization¹

Increased binding to CD16A (activating)
Decreased binding to CD32B (inhibitory)

Antibody-Dependent Cellular Cytotoxicity (ADCC)^1,³

Immune cell-mediated anti-tumor activity
Greater in vitro ADCC and NK cell activation

Fcγ=Fc gamma.

References:

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. Published online January 6, 2022. doi:10.1136/jitc-2021-003171

3. 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

4. Rugo HS, Im S, 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. Published online January 22, 2021. doi:10.1001/jamaoncol.2020.7932

The pivotal SOPHIA trial

See Efficacy

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IMPORTANT SAFETY INFORMATION

BOXED WARNING: LEFT VENTRICULAR DYSFUNCTION AND EMBRYO-FETAL TOXICITY

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.
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

Evaluate cardiac function within 4 weeks prior to and every 3 months during and upon completion of treatment.
In the pivotal SOPHIA study, 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.

Embryo-Fetal Toxicity

Based on findings in animals and mechanism of action, MARGENZA can cause fetal harm when administered to a pregnant woman.
Verify pregnancy status of women of reproductive potential prior to initiation of MARGENZA.

Infusion-Related Reactions (IRRs)

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.
In the pivotal SOPHIA study, 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.
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.

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.

Please see accompanying Full Prescribing Information, including BOXED WARNING.

IMPORTANT SAFETY INFORMATION

BOXED WARNING: LEFT VENTRICULAR DYSFUNCTION AND EMBRYO-FETAL TOXICITY

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.
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

Evaluate cardiac function within 4 weeks prior to and every 3 months during and upon completion of treatment.
In the pivotal SOPHIA study, 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.

Embryo-Fetal Toxicity

Based on findings in animals and mechanism of action, MARGENZA can cause fetal harm when administered to a pregnant woman.
Verify pregnancy status of women of reproductive potential prior to initiation of MARGENZA.

Infusion-Related Reactions (IRRs)

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.
In the pivotal SOPHIA study, 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.
Interrupt MARGENZA infusion in patients experiencing dyspnea or clinically significant hypotension. Monitor patients until symptoms completely resolve.

MOST COMMON ADVERSE REACTIONS:

Please see accompanying Full Prescribing Information, including BOXED WARNING.

INDICATION

Please see accompanying Full Prescribing Information, including BOXED WARNING.

A next generation monoclonal antibody (mAb)

MARGENZA (margetuximab-cmkb) is the first and only FDA-approved, Fc-engineered, HER2-targeted mAb designed to improve immune engagement.1,2

Mechanism of action

MARGENZA is a mAb made up of 2 functional regions.1,3

The engineered Fc region increases immune activity in vitro compared with trastuzumab1

The clinical relevance of in vitro data is unknown.

Direct Anti-Tumor Activity1

Fc Region Optimization1

Antibody-Dependent Cellular Cytotoxicity (ADCC)1,3

Direct Anti-Tumor Activity1

Fc Region Optimization1

Antibody-Dependent Cellular Cytotoxicity (ADCC)1,3

References:

Be in the know

Register for the latest information and updates about MARGENZA

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Healthcare Professionals

MARGENZA (margetuximab-cmkb) is the first and only FDA-approved, Fc-engineered, HER2-targeted mAb designed to improve immune engagement.^1,2

MARGENZA is a mAb made up of 2 functional regions.^1,³

The engineered Fc region increases immune activity in vitro compared with trastuzumab¹

Direct Anti-Tumor Activity¹

Fc Region Optimization¹

Antibody-Dependent Cellular Cytotoxicity (ADCC)^1,³

Direct Anti-Tumor Activity¹

Fc Region Optimization¹

Antibody-Dependent Cellular Cytotoxicity (ADCC)^1,³

You are now leaving the MARGENZA^® (margetuximab-cmkb) Healthcare Professionals Website.

You are now leaving the MARGENZA^® (margetuximab-cmkb) Healthcare Professionals Website.