margetuximab
{{Short description|Monoclonal antibody}}
{{Infobox drug
| type = mab
| image =
| width =
| alt =
| caption =
| mab_type = mab
| source = xi/o
| target = HER2
| pronounce =
| tradename = Margenza
| Drugs.com =
| MedlinePlus =
| DailyMedID = Margetuximab
| pregnancy_AU =
| pregnancy_AU_comment =
| pregnancy_category= Not recommended. Margetuximab can cause fetal harm when administered to a pregnant woman.
| routes_of_administration = Intravenous
| class = HER2/neu receptor antagonist
| ATC_prefix = L01
| ATC_suffix = FD06
| ATC_supplemental =
| legal_AU =
| legal_AU_comment =
| legal_BR =
| legal_BR_comment =
| legal_CA =
| legal_CA_comment =
| legal_DE =
| legal_DE_comment =
| legal_NZ =
| legal_NZ_comment =
| legal_UK =
| legal_UK_comment =
| legal_US = Rx-only
| legal_US_comment = {{cite web | title = Margenza FDA label | url = https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/761150s000lbl.pdf}}{{cite web | title=FDA approves margetuximab for metastatic HER2-positive breast cancer | website=U.S. Food and Drug Administration (FDA) | date=16 December 2020 | url=http://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-margetuximab-metastatic-her2-positive-breast-cancer | access-date=25 December 2020}} {{PD-notice}}
| legal_EU =
| legal_EU_comment =
| legal_UN =
| legal_UN_comment =
| legal_status =
| bioavailability =
| protein_bound =
| metabolism =
| metabolites =
| onset =
| elimination_half-life =
| duration_of_action =
| excretion =
| CAS_number_Ref =
| CAS_number = 1350624-75-7
| CAS_supplemental =
| PubChem =
| IUPHAR_ligand =
| DrugBank_Ref =
| DrugBank = DB14967
| ChemSpiderID_Ref =
| ChemSpiderID = None
| UNII_Ref = {{fdacite|correct|FDA}}
| UNII = K911R84KEW
| KEGG_Ref =
| KEGG = D10446
| ChEBI_Ref =
| ChEBI =
| ChEMBL_Ref =
| ChEMBL =
| NIAID_ChemDB =
| PDB_ligand =
| synonyms = margetuximab-cmkb, MGAH22
| IUPAC_name =
| C=6484 | H=10010 | N=1726 | O=2024 | S=42
| SMILES =
| StdInChI =
| StdInChI_comment =
| StdInChIKey =
| density =
| density_notes =
| melting_point =
| melting_high =
| melting_notes =
| boiling_point =
| boiling_notes =
| solubility =
| sol_units =
| specific_rotation =
}}
Margetuximab, sold under the brand name Margenza, is a chimeric IgG monoclonal antibody medication against HER2 used for the treatment of cancer.[http://www.ama-assn.org/resources/doc/usan/margetuximab.pdf Statement On A Nonproprietary Name Adopted By The USAN Council - Margetuximab], American Medical Association.{{cite web | title=Margenza | work=NCI Drug Dictionary | publisher=National Cancer Institute | url=https://www.cancer.gov/publications/dictionaries/cancer-drug/def/margetuximab | access-date=17 December 2020}}
The most common adverse drug reactions 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.
This drug was created by Raven biotechnologies, which was later acquired by MacroGenics. It was engineered to increase affinity for CD16A polymorphisms and decrease affinity for FcγRIIB (CD32B), an inhibitory receptor.
It binds to the same target (epitope) as trastuzumab,{{Cite web |url=http://www.targetedonc.com/news/pegram-discusses-promise-of-margetuximabchemo-combo-for-her2-breast-cancer |title=Pegram Discusses Promise of Margetuximab/Chemo Combo for HER2+ Breast Cancer. Jan 2017 |access-date=2017-02-27 |archive-date=2018-07-31 |archive-url=https://web.archive.org/web/20180731111202/https://www.targetedonc.com/news/pegram-discusses-promise-of-margetuximabchemo-combo-for-her2-breast-cancer |url-status=dead }} on the HER2 receptor.
Medical uses
Margetuximab is indicated, in combination with chemotherapy, for the treatment of adults 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.{{cite journal | vauthors = Markham A | title = Margetuximab: First Approval | journal = Drugs | volume = 81| issue = 5| pages = 599–604| date = March 2021 | pmid = 33761116 | doi = 10.1007/s40265-021-01485-2 | s2cid = 232329257 }}
History
It is in phase III clinical trials for combination therapy in metastatic breast cancer{{ClinicalTrialsGov|NCT02492711}} in collaboration with Merck.{{cite web | title = MacroGenics and Merck to Collaborate on Immuno-Oncology Study Evaluating Margetuximab in Combination with KEYTRUDA® (pembrolizumab) for Advanced Gastric Cancer | url = http://www.mercknewsroom.com/news-release/prescription-medicine-news/macrogenics-and-merck-collaborate-immuno-oncology-study-eval | archive-url = https://web.archive.org/web/20170510205146/http://www.mercknewsroom.com/news-release/prescription-medicine-news/macrogenics-and-merck-collaborate-immuno-oncology-study-eval | archive-date = 10 May 2017 | publisher = Merck & Co., Inc }} Phase II trials are also in progress for gastric cancer and esophageal cancer.{{ClinicalTrialsGov|NCT02689284}}{{update inline|date=December 2020}}
In June 2020, it received orphan drug designation from the U.S. Food and Drug Administration (FDA).{{cite web | title=Margetuximab Orphan Drug Designations and Approvals | website=U.S. Food and Drug Administration (FDA) | date=3 June 2020 | url=https://www.accessdata.fda.gov/scripts/opdlisting/oopd/detailedIndex.cfm?cfgridkey=739820 | archive-url=https://web.archive.org/web/20200607033435/https://www.accessdata.fda.gov/scripts/opdlisting/oopd/detailedIndex.cfm?cfgridkey=739820 | url-status=dead | archive-date=June 7, 2020 | access-date=6 June 2020}}
Efficacy was evaluated in SOPHIA (NCT02492711), a randomized, multicenter, open-label trial of 536 participants with IHC 3+ or ISH-amplified HER2+ metastatic breast cancer who had received prior treatment with other anti-HER2 therapies.{{cite web | title=Drug Trials Snapshot: Margenza | website=U.S. Food and Drug Administration (FDA) | date=16 December 2020 | url=https://www.fda.gov/drugs/drug-approvals-and-databases/drug-trials-snapshot-margenza | access-date=6 January 2021}} {{PD-notice}} Participants were randomized (1:1) to margetuximab plus chemotherapy or trastuzumab plus chemotherapy. Randomization was stratified by chemotherapy choice (capecitabine, eribulin, gemcitabine, or vinorelbine), number of lines of therapy in the metastatic setting (≤ 2, > 2), and number of metastatic sites (≤ 2, > 2). The trial was conducted at 166 sites in the United States and 16 other countries.
It was approved for medical use in the United States in December 2020.{{cite web | title=Margenza: FDA-Approved Drugs | website=U.S. Food and Drug Administration (FDA) | url=https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&ApplNo=761150 | access-date=17 December 2020}}{{dead link|date=May 2025|bot=medic}}{{cbignore|bot=medic}}
References
{{reflist}}
{{Targeted cancer therapeutic agents}}
{{Monoclonals for tumors}}
{{Portal bar | Medicine}}