Peringatan Keamanan

Toxicity information regarding margetuximab is not readily available. Patients experiencing an overdose are at an increased risk of severe adverse effects such as infusion-related reactions. Symptomatic and supportive measures are recommended.L27986

Margetuximab

DB14967

biotech approved investigational

Deskripsi

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.A225751 The introduction of trastuzumab improved patient outcomes in HER2-positive breast cancer, but notably depended substantially on polymorphisms in the Fc?RIIIA/CD16A receptor, whereby low affinity 158F CD16A variants are associated with shorter progression-free survival and worse patient outcomes.A225756

Margetuximab (formerly MGAH22) is an Fc-engineered human/mouse chimeric anti-HER2 IgG1? monoclonal antibody derived from the same mouse 4D5 clone that trastuzumab is derived from and is produced in Chinese Hamster Ovary (CHO) culture.A225751, A225756, A225766, A191829, L27986 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.A225751, A225756, A225766, A191829, L27986

Margextuximab was granted FDA approval on December 16, 2020, and is currently marketed under the trademark MARGENZA™ by MacroGenics, Inc.L27986

Struktur Molekul 2D

Struktur tidak tersedia

Peta Jejaring Molekuler
Legenda: ObatTargetGenEnzim(Panah → menunjukkan arah efek / relasi)TransporterCarrier

Profil Farmakokinetik

Waktu Paruh (Half-Life) Margetuximab has a geometric mean (%CV) terminal half-life of 19.2 (28%) days.[L27986]
Volume Distribusi Margetuximab has a geometric mean (%CV) volume of distribution of 5.47 (22%) L.[L27986]
Klirens (Clearance) Margetuximab has a geometric mean (%CV) clearance of 0.22 (24%) L/day. Four months following margetuximab discontinuation, the concentration is approximately 3% of the steady-state trough serum concentration.[L27986]

Absorpsi

In patients with HER2-positive relapsed or refractory breast cancer, margetuximab administered at the recommended dose results in a steady-state geometric mean (%CV) Cmax of 466 (20%) ?g/mL and an AUC0-21d of 4120 (21%) ?g\*day/mL. After a single dose, the Cmax and AUC0-21d increase in a dose-proportional manner from 10 to 18 mg/kg, which is 0.67 to 1.2 times the recommended dose. The time to steady-state is two months at the recommended dosage, and the accumulation ratio is 1.65 based on the AUC0-21d. There are no significant effects on margetuximab exposure by altering the infusion time in the range of 30 minutes to 120 minutes.L27986

Metabolisme

Like other monoclonal antibodies, margetuximab is expected to be metabolized into smaller peptides through various proteases and catabolic pathways.L27986

Rute Eliminasi

Data eliminasi belum tersedia.

Interaksi Obat

425 Data
Diethylstilbestrol Diethylstilbestrol may increase the thrombogenic activities of Margetuximab.
Chlorotrianisene Chlorotrianisene may increase the thrombogenic activities of Margetuximab.
Conjugated estrogens Conjugated estrogens may increase the thrombogenic activities of Margetuximab.
Estrone Estrone may increase the thrombogenic activities of Margetuximab.
Estradiol Estradiol may increase the thrombogenic activities of Margetuximab.
Dienestrol Dienestrol may increase the thrombogenic activities of Margetuximab.
Ethinylestradiol Ethinylestradiol may increase the thrombogenic activities of Margetuximab.
Mestranol Mestranol may increase the thrombogenic activities of Margetuximab.
Estriol Estriol may increase the thrombogenic activities of Margetuximab.
Estrone sulfate Estrone sulfate may increase the thrombogenic activities of Margetuximab.
Quinestrol Quinestrol may increase the thrombogenic activities of Margetuximab.
Hexestrol Hexestrol may increase the thrombogenic activities of Margetuximab.
Tibolone Tibolone may increase the thrombogenic activities of Margetuximab.
Synthetic Conjugated Estrogens, A Synthetic Conjugated Estrogens, A may increase the thrombogenic activities of Margetuximab.
Synthetic Conjugated Estrogens, B Synthetic Conjugated Estrogens, B may increase the thrombogenic activities of Margetuximab.
Polyestradiol phosphate Polyestradiol phosphate may increase the thrombogenic activities of Margetuximab.
Esterified estrogens Esterified estrogens may increase the thrombogenic activities of Margetuximab.
Zeranol Zeranol may increase the thrombogenic activities of Margetuximab.
Equol Equol may increase the thrombogenic activities of Margetuximab.
Promestriene Promestriene may increase the thrombogenic activities of Margetuximab.
Methallenestril Methallenestril may increase the thrombogenic activities of Margetuximab.
Epimestrol Epimestrol may increase the thrombogenic activities of Margetuximab.
Moxestrol Moxestrol may increase the thrombogenic activities of Margetuximab.
Estradiol acetate Estradiol acetate may increase the thrombogenic activities of Margetuximab.
Estradiol benzoate Estradiol benzoate may increase the thrombogenic activities of Margetuximab.
Estradiol cypionate Estradiol cypionate may increase the thrombogenic activities of Margetuximab.
Estradiol valerate Estradiol valerate may increase the thrombogenic activities of Margetuximab.
Biochanin A Biochanin A may increase the thrombogenic activities of Margetuximab.
Formononetin Formononetin may increase the thrombogenic activities of Margetuximab.
Estetrol Estetrol may increase the thrombogenic activities of Margetuximab.
Cetuximab The risk or severity of adverse effects can be increased when Cetuximab is combined with Margetuximab.
Human immunoglobulin G The risk or severity of adverse effects can be increased when Human immunoglobulin G is combined with Margetuximab.
Omalizumab The risk or severity of adverse effects can be increased when Omalizumab is combined with Margetuximab.
Adalimumab The risk or severity of adverse effects can be increased when Adalimumab is combined with Margetuximab.
Abciximab The risk or severity of adverse effects can be increased when Abciximab is combined with Margetuximab.
Gemtuzumab ozogamicin The risk or severity of adverse effects can be increased when Gemtuzumab ozogamicin is combined with Margetuximab.
Indium In-111 satumomab pendetide The risk or severity of adverse effects can be increased when Indium In-111 satumomab pendetide is combined with Margetuximab.
Infliximab The risk or severity of adverse effects can be increased when Infliximab is combined with Margetuximab.
Trastuzumab The risk or severity of adverse effects can be increased when Trastuzumab is combined with Margetuximab.
Rituximab The risk or severity of adverse effects can be increased when Rituximab is combined with Margetuximab.
Basiliximab The risk or severity of adverse effects can be increased when Basiliximab is combined with Margetuximab.
Muromonab The risk or severity of adverse effects can be increased when Muromonab is combined with Margetuximab.
Digoxin Immune Fab (Ovine) The risk or severity of adverse effects can be increased when Digoxin Immune Fab (Ovine) is combined with Margetuximab.
Ibritumomab tiuxetan The risk or severity of adverse effects can be increased when Ibritumomab tiuxetan is combined with Margetuximab.
Tositumomab The risk or severity of adverse effects can be increased when Tositumomab is combined with Margetuximab.
Alemtuzumab The risk or severity of adverse effects can be increased when Alemtuzumab is combined with Margetuximab.
Capromab pendetide The risk or severity of adverse effects can be increased when Capromab pendetide is combined with Margetuximab.
Efalizumab The risk or severity of adverse effects can be increased when Efalizumab is combined with Margetuximab.
Antithymocyte immunoglobulin (rabbit) The risk or severity of adverse effects can be increased when Antithymocyte immunoglobulin (rabbit) is combined with Margetuximab.
Natalizumab The risk or severity of adverse effects can be increased when Natalizumab is combined with Margetuximab.
Palivizumab The risk or severity of adverse effects can be increased when Palivizumab is combined with Margetuximab.
Daclizumab The risk or severity of adverse effects can be increased when Daclizumab is combined with Margetuximab.
Bevacizumab The risk or severity of adverse effects can be increased when Bevacizumab is combined with Margetuximab.
Technetium Tc-99m arcitumomab The risk or severity of adverse effects can be increased when Technetium Tc-99m arcitumomab is combined with Margetuximab.
Eculizumab The risk or severity of adverse effects can be increased when Eculizumab is combined with Margetuximab.
Panitumumab The risk or severity of adverse effects can be increased when Panitumumab is combined with Margetuximab.
Ranibizumab The risk or severity of adverse effects can be increased when Ranibizumab is combined with Margetuximab.
Galiximab The risk or severity of adverse effects can be increased when Galiximab is combined with Margetuximab.
Pexelizumab The risk or severity of adverse effects can be increased when Pexelizumab is combined with Margetuximab.
Afelimomab The risk or severity of adverse effects can be increased when Afelimomab is combined with Margetuximab.
Epratuzumab The risk or severity of adverse effects can be increased when Epratuzumab is combined with Margetuximab.
Bectumomab The risk or severity of adverse effects can be increased when Bectumomab is combined with Margetuximab.
Oregovomab The risk or severity of adverse effects can be increased when Oregovomab is combined with Margetuximab.
IGN311 The risk or severity of adverse effects can be increased when IGN311 is combined with Margetuximab.
Adecatumumab The risk or severity of adverse effects can be increased when Adecatumumab is combined with Margetuximab.
Labetuzumab The risk or severity of adverse effects can be increased when Labetuzumab is combined with Margetuximab.
Matuzumab The risk or severity of adverse effects can be increased when Matuzumab is combined with Margetuximab.
Fontolizumab The risk or severity of adverse effects can be increased when Fontolizumab is combined with Margetuximab.
Bavituximab The risk or severity of adverse effects can be increased when Bavituximab is combined with Margetuximab.
CR002 The risk or severity of adverse effects can be increased when CR002 is combined with Margetuximab.
Rozrolimupab The risk or severity of adverse effects can be increased when Rozrolimupab is combined with Margetuximab.
Girentuximab The risk or severity of adverse effects can be increased when Girentuximab is combined with Margetuximab.
Obiltoxaximab The risk or severity of adverse effects can be increased when Obiltoxaximab is combined with Margetuximab.
XTL-001 The risk or severity of adverse effects can be increased when XTL-001 is combined with Margetuximab.
NAV 1800 The risk or severity of adverse effects can be increased when NAV 1800 is combined with Margetuximab.
Briakinumab The risk or severity of adverse effects can be increased when Briakinumab is combined with Margetuximab.
Otelixizumab The risk or severity of adverse effects can be increased when Otelixizumab is combined with Margetuximab.
AMG 108 The risk or severity of adverse effects can be increased when AMG 108 is combined with Margetuximab.
Iratumumab The risk or severity of adverse effects can be increased when Iratumumab is combined with Margetuximab.
Enokizumab The risk or severity of adverse effects can be increased when Enokizumab is combined with Margetuximab.
Ramucirumab The risk or severity of adverse effects can be increased when Ramucirumab is combined with Margetuximab.
Farletuzumab The risk or severity of adverse effects can be increased when Farletuzumab is combined with Margetuximab.
Veltuzumab The risk or severity of adverse effects can be increased when Veltuzumab is combined with Margetuximab.
Ustekinumab The risk or severity of adverse effects can be increased when Ustekinumab is combined with Margetuximab.
Trastuzumab emtansine The risk or severity of adverse effects can be increased when Trastuzumab emtansine is combined with Margetuximab.
PRO-542 The risk or severity of adverse effects can be increased when PRO-542 is combined with Margetuximab.
TNX-901 The risk or severity of adverse effects can be increased when TNX-901 is combined with Margetuximab.
Inotuzumab ozogamicin The risk or severity of adverse effects can be increased when Inotuzumab ozogamicin is combined with Margetuximab.
RI 624 The risk or severity of adverse effects can be increased when RI 624 is combined with Margetuximab.
Stamulumab The risk or severity of adverse effects can be increased when MYO-029 is combined with Margetuximab.
CT-011 The risk or severity of adverse effects can be increased when CT-011 is combined with Margetuximab.
Leronlimab The risk or severity of adverse effects can be increased when Leronlimab is combined with Margetuximab.
Glembatumumab vedotin The risk or severity of adverse effects can be increased when Glembatumumab vedotin is combined with Margetuximab.
Olaratumab The risk or severity of adverse effects can be increased when Olaratumab is combined with Margetuximab.
IPH 2101 The risk or severity of adverse effects can be increased when IPH 2101 is combined with Margetuximab.
TB-402 The risk or severity of adverse effects can be increased when TB-402 is combined with Margetuximab.
Caplacizumab The risk or severity of adverse effects can be increased when Caplacizumab is combined with Margetuximab.
IMC-1C11 The risk or severity of adverse effects can be increased when IMC-1C11 is combined with Margetuximab.
Eldelumab The risk or severity of adverse effects can be increased when Eldelumab is combined with Margetuximab.
Lumiliximab The risk or severity of adverse effects can be increased when Lumiliximab is combined with Margetuximab.

Target Protein

Receptor tyrosine-protein kinase erbB-2 ERBB2

Referensi & Sumber

Synthesis reference: Nordstrom JL, Gorlatov S, Zhang W, Yang Y, Huang L, Burke S, Li H, Ciccarone V, Zhang T, Stavenhagen J, Koenig S, Stewart SJ, Moore PA, Johnson S, Bonvini E: Anti-tumor activity and toxicokinetics analysis of MGAH22, an anti-HER2 monoclonal antibody with enhanced Fcgamma receptor binding properties. Breast Cancer Res. 2011;13(6):R123. doi: 10.1186/bcr3069.
Artikel (PubMed)
  • PMID: 32368385
    Kreutzfeldt J, Rozeboom B, Dey N, De P: The trastuzumab era: current and upcoming targeted HER2+ breast cancer therapies. Am J Cancer Res. 2020 Apr 1;10(4):1045-1067. eCollection 2020.
  • PMID: 22129105
    Nordstrom JL, Gorlatov S, Zhang W, Yang Y, Huang L, Burke S, Li H, Ciccarone V, Zhang T, Stavenhagen J, Koenig S, Stewart SJ, Moore PA, Johnson S, Bonvini E: Anti-tumor activity and toxicokinetics analysis of MGAH22, an anti-HER2 monoclonal antibody with enhanced Fcgamma receptor binding properties. Breast Cancer Res. 2011;13(6):R123. doi: 10.1186/bcr3069. Epub 2011 Nov 30.
  • PMID: 28119295
    Bang YJ, Giaccone G, Im SA, Oh DY, Bauer TM, Nordstrom JL, Li H, Chichili GR, Moore PA, Hong S, Stewart SJ, Baughman JE, Lechleider RJ, Burris HA: 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 Apr 1;28(4):855-861. doi: 10.1093/annonc/mdx002.
  • PMID: 31847708
    Kaplon H, Muralidharan M, Schneider Z, Reichert JM: Antibodies to watch in 2020. MAbs. 2020 Jan-Dec;12(1):1703531. doi: 10.1080/19420862.2019.1703531.

Contoh Produk & Brand

Produk: 1 • International brands: 1
Produk
  • Margenza
    Injection, solution, concentrate • 25 mg/1mL • Intravenous • US • Approved
International Brands
  • Margenza — MacroGenics, Inc.

Sekuens Gen/Protein (FASTA)

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