Margetuximab

Overview

The HER2 oncoprotein, the product of the human ERBB2/mouse neu genes, is a member of the HER family of receptor tyrosine kinases that includes the epidermal growth factor receptor (EGFR). Of the various subtypes of breast cancer, HER2-positive breast cancer is characterized by ERBB2 overexpression, a higher grade, a more aggressive phenotype, and a worse prognosis compared to HER2-negative cancer. The introduction of trastuzumab improved patient outcomes in HER2-positive breast cancer, but notably depended substantially on polymorphisms in the FcγRIIIA/CD16A receptor, whereby low affinity 158F CD16A variants are associated with shorter progression-free survival and worse patient outcomes. Margetuximab (formerly MGAH22) is an Fc-engineered human/mouse chimeric anti-HER2 IgG1κ monoclonal antibody derived from the same mouse 4D5 clone that trastuzumab is derived from and is produced in Chinese Hamster Ovary (CHO) culture. Margetuximab binds to the same epitope on the HER2 extracellular domain and induces the same effects as trastuzumab. However, due to its modified Fc region, margetuximab binds with higher affinity to both CD16A variants and exhibits weaker binding to the inhibitory CD32B Fc receptor, resulting in more efficient antibody-dependent cell-mediated cytotoxicity (ADCC) and increased efficacy compared to trastuzumab. Margextuximab was granted FDA approval on December 16, 2020, and is currently marketed under the trademark MARGENZA™ by MacroGenics, Inc.

Indication

Margetuximab is an anti-HER2 monoclonal antibody indicated, in combination with chemotherapy, for the treatment of metastatic HER2-positive breast cancer in adult patients who have received two or more prior anti-HER2 regimens with at least one prior regimen for metastatic disease.

Associated Conditions

Metastatic Breast Cancer With HER2 Positive

Clinical Trials

Title	Posted	Study ID	Phase	Status	Sponsor
Margetuximab Plus Tucatinib and Capecitabine in HER2-positive Metastatic Breast Cancer	2022/02/07	NCT05227131	Phase 2	Withdrawn	MedSIR
MARGetuximab Or Trastuzumab (MARGOT)	2020/06/11	NCT04425018	Phase 2	Active, not recruiting	Dana-Farber Cancer Institute
A Study to Evaluate the Pharmacokinetics of Margetuximab in Chinese Patients With HER2+ MBC	2020/05/21	NCT04398108	Phase 1	Completed	Zai Lab (Shanghai) Co., Ltd.
A Study to Evaluate the Efficacy and Safety of Margetuximab Plus Chemotherapy in the Treatment of Chinese Patients With HER2+ MBC	2020/02/10	NCT04262804	Phase 2	Active, not recruiting	Zai Lab (Shanghai) Co., Ltd.
Combination Margetuximab, Retifanlimab, Tebotelimab, and Chemotherapy Phase 2/3 Trial in HER2+ Gastric/GEJ Cancer	2019/09/09	NCT04082364	Phase 2	Completed	MacroGenics
Margetuximab Expanded Access Program	2017/04/28	NCT03133988	N/A	APPROVED_FOR_MARKETING	TerSera Therapeutics LLC
Margetuximab Plus Chemotherapy vs Trastuzumab Plus Chemotherapy in the Treatment of HER2+ Metastatic Breast Cancer	2015/07/09	NCT02492711	Phase 3	Completed	MacroGenics
Phase 2 Study of the Monoclonal Antibody MGAH22 (Margetuximab) in Patients With Relapsed or Refractory Advanced Breast Cancer	2013/04/10	NCT01828021	Phase 2	Completed	MacroGenics
Safety Study of MGAH22 in HER2-positive Carcinomas	2010/06/22	NCT01148849	Phase 1	Completed	MacroGenics

FDA Drug Approvals

Approved Product	Manufacturer	NDC Code	Route	Strength	Effective Date
MARGENZA	MacroGenics, Inc	74527-022	INTRAVENOUS	25 mg in 1 mL	5/30/2023

EMA Drug Approvals

Approved Product	Authorization Holder	Status	Issued Date
No EMA approvals found for this drug.

HSA Drug Approvals

Approved Product	Manufacturer	Approval Number	Dosage Form	Strength	Approval Date
No HSA approvals found for this drug.

NMPA Drug Approvals

Approved Product	Company	Approval Number	Drug Type	Dosage Form	Approval Date
No NMPA approvals found for this drug.

PPB Drug Approvals

Approved Product	Registration No.	Company	Licence No.	Strength	Registration Date
No PPB approvals found for this drug.

TGA Drug Approvals

Approved Product	ARTG ID	Sponsor	Registration Type	Status	Registration Date
No TGA approvals found for this drug.

Health Canada Drug Approvals

Approved Product	Company	DIN	Dosage Form	Strength	Market Date
No Health Canada approvals found for this drug.

CIMA AEMPS Drug Approvals

Approved Product	Company	Registration Number	Pharmaceutical Form	Prescription Type	Status
No CIMA AEMPS (Spain) approvals found for this drug.

Philippines FDA Drug Approvals

Approved Product	Company	License Number	Dosage Form	Strength	Approval Date
No Philippines FDA approvals found for this drug.

Saudi SFDA Drug Approvals

Approved Product	Company	License Number	Dosage Form	Strength	Approval Date
No Saudi SFDA approvals found for this drug.

Malaysia NPRA Drug Approvals

Approved Product	Company	Registration Number	Dosage Form	Strength	Approval Date
No Malaysia NPRA approvals found for this drug.

UK EMC Drug Information

Medicine Name	MA Holder	MA Number	Pharmaceutical Form	Active Ingredient	Authorization Date
No UK EMC drug information found for this drug.

Related News

MARGOT Trial: Margetuximab Shows Numerical, but Not Significant, Improvement in HER2-Positive Breast Cancer

7 months ago

• The MARGOT phase II trial compared margetuximab plus paclitaxel and pertuzumab (TMP) to trastuzumab plus paclitaxel and pertuzumab (THP) in neoadjuvant treatment of stage II-III HER2-positive breast cancer. • While the TMP regimen showed a 10% numerical increase in pathologic complete response (pCR) rate compared to THP, the difference was not statistically significant. • In hormone receptor-positive, HER2-positive patients, TMP showed a 19% increase in pCR rate compared to THP, trending towards statistical significance but not meeting the threshold. • Further analysis of the tumor immune microenvironment is planned to identify potential biomarkers for patient selection to optimize margetuximab's efficacy.

Novel Bispecific Immunotherapy Shows Promise Across Multiple Cancer Types in Early Clinical Trial

2 years ago

A novel bispecific immunotherapy drug, tebotelimab, demonstrated encouraging response rates across multiple advanced cancer types by simultaneously blocking PD-1 and LAG-3 immune checkpoints in a 269-patient international trial.

Margetuximab Shows Promise as Alternative Therapy in HER2-Positive Advanced Breast Cancer

2 years ago

Margetuximab, a second-generation anti-HER2 antibody, has shown potential as a later-line therapy for HER2-positive advanced breast cancer.

Margetuximab Fails to Show Overall Survival Benefit Over Trastuzumab in HER2-Positive Breast Cancer

3 years ago

• Final overall survival (OS) results from the phase 3 SOPHIA trial showed margetuximab plus chemotherapy did not significantly improve OS compared to trastuzumab plus chemotherapy in HER2-positive advanced breast cancer. • Median OS was 21.6 months for margetuximab vs. 21.9 months for trastuzumab (HR 0.95; P = .620), with similar OS rates at 12, 18, and 24 months between the two arms. • A subgroup analysis suggested a potential OS benefit with margetuximab in patients carrying the CD16A-158F low-affinity allele, warranting further investigation. • Margetuximab remains a treatment option for pretreated HER2-positive advanced breast cancer, but the study highlights the need for biomarker-driven patient selection.

Margetuximab Not Cost-Effective Compared to Trastuzumab for ERBB2-Positive Advanced Breast Cancer