Peringatan Keamanan

Toxicity information regarding mirvetuximab soravtansine-gynx is not readily available. Patients experiencing an overdose are at an increased risk of severe adverse effects such as ocular toxicity, pneumonitis and peripheral neuropathy.^L43967 Symptomatic and supportive measures are recommended.

Carcinogenicity studies with mirvetuximab soravtansine-gynx or DM4 have not been performed. An in vivo rat bone marrow micronucleus study showed that DM4 and its metabolite, S-methyl DM4, are clastogenic. DM4 and S-methyl DM4 did not show evidence of mutagenicity in the bacterial reverse mutation (Ames) assay. The effects of mirvetuximab soravtansine-gynx or DM4 on fertility studies have not been evaluated.^L43967

Mirvetuximab soravtansine

DB12489

biotech approved investigational

Deskripsi

Mirvetuximab soravtansine-gynx (IMGN853) is an antibody-drug conjugate (ADC) formed by a monoclonal antibody (M9346A) that targets folate receptor alpha (FR?), covalently joined by a cleavable disulfide linker to the genotoxic compound DM4 (also known as soravtansine or ravtansine).A254392,L43967 DM4 is conjugated to the antibody with a drug-to-antibody ratio of 3.5:1.^A254387

The antibody component of mirvetuximab soravtansine-gynx binds to FR?, a receptor overexpressed on the surface of epithelial tumor cells, characteristic of ovarian, endometrial, triple-negative breast and non-small-cell lung cancers.^A254382 After an ADC/receptor complex is formed, mirvetuximab soravtansine-gynx is internalized, and DM4 is released inside the cell. DM4 leads to cell-cycle arrest and apoptosis and is also able to diffuse into neighboring cells and induce further cell death.^A254382

On November 2022, the FDA granted accelerated approval to mirvetuximab soravtansine-gynx for the treatment of adult patients with FR?–positive, platinum-resistant epithelial ovarian, fallopian tube, or primary peritoneal cancer who have received 1-3 prior systemic treatment regimens. This decision was supported by findings from the phase 3 SORAYA trial (NCT04296890).L43967,L43972 It was subsequently granted full approval in March 2024.^L50306

Struktur Molekul 2D

Struktur tidak tersedia

Peta Jejaring Molekuler

Obat Target Gen Interaksi Enzim Transporter Carrier

Legenda: Obat • Target • Gen • Enzim • (Panah → menunjukkan arah efek / relasi) • Transporter • Carrier

1. Pendahuluan & Konsep

Fitur visualisasi ini dikembangkan menggunakan pendekatan Graph Theory untuk memetakan hubungan polifarmasi dan molekuler. Entitas (Obat, Target, Gen) direpresentasikan sebagai Simpul (Nodes), sedangkan hubungan biologisnya sebagai Sisi (Edges).

2. Sumber Data (Validasi)

Data Obat: Diekstraksi dari elemen drugbank-id dan name pada skema XML DrugBank.
Target Protein: Diambil dari elemen targets/target yang memuat polipeptida sasaran.
Genetik: Disinkronisasi dari sub-elemen gene-name dan varian snp-effects.
Genetik: Jumlah titik node dibatasi pada maksimal 10 (Slice=10) interaksi untuk menghindari tumpukan data.

3. Algoritma Visualisasi

Tata letak grafik menggunakan algoritma Force-Directed Graph (Barnes-Hut). Model fisika ini menerapkan gaya tolak-menolak antar simpul (Gravitasi: -3000) agar tidak tumpang tindih, serta gaya pegas (Spring: 0.04) pada garis penghubung untuk fleksibilitas interaksi.

4. Legenda Visual

Obat Utama (Pusat Analisis)

Target Protein (Mekanisme)

Gen (Faktor Genetik)

Metode ini mendukung analisis Precision Medicine dan evaluasi risiko Drug-Drug Interaction (DDI).

Profil Farmakokinetik

Waktu Paruh (Half-Life) After the first dose, the geometric mean terminal phase half-life of mirvetuximab soravtansine-gynx is 4.8 days.[L43967] The geometric mean terminal phase half-lives of the unconjugated DM4 and its metabolite, S-methyl-DM4, are 2.8 and 5.0 days, respectively.[L43967]

Volume Distribusi Mirvetuximab soravtansine-gynx has a steady-state volume of distribution of 2.63 L.[L43967]

Klirens (Clearance) The total plasma clearance of mirvetuximab soravtansine-gynx is 18.9 mL/hour.[L43967] The unconjugated DM4 has a total plasma clearance of 13.8 L/hour, while its metabolite, S-methyl-DM4, has a total plasma clearance of 4.3 L/hour.[L43967]

Absorpsi

The pharmacokinetic parameters of mirvetuximab soravtansine-gynx were evaluated in patients given a 6 mg/kg adjusted ideal body weight (AIBW) dose administered during the first treatment cycle (3 weeks). Mirvetuximab Soravtansine-gynx, the unconjugated DM4, and S-methyl-DM4 had a corresponding C_max of 137.3 µg/mL, 4.11 ng/mL and 6.98 ng/mL, and a corresponding AUC_tau of 20.65 h?mg/mL, 530 h?ng/mL and 1848 h?ng/mL.^L43967 The peak concentration of mirvetuximab soravtansine-gynx was observed near the end of intravenous infusion, while DM4 and S-methyl-DM4 concentrations peaked 2 and 3 days after mirvetuximab soravtansine-gynx administration. After one treatment cycle, mirvetuximab soravtansine-gynx, DM4, and S-methyl-DM4 reached steady-state concentrations. Following the repeated administration of mirvetuximab soravtansine-gynx, the accumulation of mirvetuximab soravtansine-gynx, DM4, and S-methyl-DM4 were minimal.^L43967

Metabolisme

After mirvetuximab soravtansine-gynx binds the folate receptor alpha (FR?) and is internalized via antigen-mediated endocytosis, the DM4 agent is released via proteolytic cleavage. The monoclonal antibody portion of this drug is expected to be metabolized by catabolic pathways into small peptides. Unconjugated DM4 is reduced and S-methylated to form S-methyl-DM4. DM4 and S-methyl-DM4 are the main circulating metabolites of mirvetuximab soravtansine-gynx and correspond to approximately 0.4% and 1.4% of mirvetuximab soravtansine-gynx AUCs. Both DM4 and S-methyl-DM4 undergo metabolism by CYP3A4.^L43967

Rute Eliminasi

Mirvetuximab soravtansine-gynx metabolites S-methyl DM4 and DM4-sulfo-SPDB-lysine were detected in urine within 24 hours of infusion as the main metabolites.^L43967

Interaksi Obat

449 Data

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

Target Protein

Folate receptor alpha FOLR1

Referensi & Sumber

Synthesis reference: Payne, G. et al. (2016). Methods for formulating antibody drug conjugate compositions. World Intellectual Property Organization WO 2016/036861 A1. Available at: https://patentimages.storage.googleapis.com/81/ac/da/92f7eb5933228f/WO2016036861A1.pdf

Artikel (PubMed)

PMID: 29098867
Moore KN, Martin LP, O'Malley DM, Matulonis UA, Konner JA, Vergote I, Ponte JF, Birrer MJ: A review of mirvetuximab soravtansine in the treatment of platinum-resistant ovarian cancer. Future Oncol. 2018 Jan;14(2):123-136. doi: 10.2217/fon-2017-0379. Epub 2017 Nov 3.
PMID: 36046840
Nerone M, Grande MD, Sessa C, Colombo I: Advancing antibody-drug conjugates in gynecological malignancies: myth or reality? Explor Target Antitumor Ther. 2022;3(2):149-171. doi: 10.37349/etat.2022.00077. Epub 2022 Apr 19.
PMID: 34683998
Martin-Sabroso C, Lozza I, Torres-Suarez AI, Fraguas-Sanchez AI: Antibody-Antineoplastic Conjugates in Gynecological Malignancies: Current Status and Future Perspectives. Pharmaceutics. 2021 Oct 15;13(10). pii: pharmaceutics13101705. doi: 10.3390/pharmaceutics13101705.
PMID: 25904506
Ab O, Whiteman KR, Bartle LM, Sun X, Singh R, Tavares D, LaBelle A, Payne G, Lutz RJ, Pinkas J, Goldmacher VS, Chittenden T, Lambert JM: IMGN853, a Folate Receptor-alpha (FRalpha)-Targeting Antibody-Drug Conjugate, Exhibits Potent Targeted Antitumor Activity against FRalpha-Expressing Tumors. Mol Cancer Ther. 2015 Jul;14(7):1605-13. doi: 10.1158/1535-7163.MCT-14-1095. Epub 2015 Apr 22.

Link

Contoh Produk & Brand

Produk: 1 • International brands: 1

Produk

Elahere

Injection, solution • 5 mg/1mL • Intravenous • US • Approved

International Brands

Elahere — ImmunoGen, Inc.

Sekuens Gen/Protein (FASTA)

Sekuens dimuat saat dibutuhkan agar halaman tetap ringan.