Mirvetuximab soravtansine
生产企业：AbbVie
Mirvetuximab soravtansine is a folate receptor alpha-directed antibody and microtubule inhibitor conjugate used to treat folate receptor alpha positive, platinum-resistant epithelial ovarian, fallopian tube, or primary peritoneal cancer.
Mirvetuximab soravtansine is a folate receptor alpha-directed antibody and microtubule inhibitor conjugate used to treat folate receptor alpha positive, platinum-resistant epithelial ovarian, fallopian tube, or primary peritoneal cancer.
Mirvetuximab soravtansine-gynx is an antibody-drug conjugate (ADC) formed by three components: a chimeric IgG1 antibody against folate receptor alpha (FRα), the small molecule anti-tubulin agent DM4 (a maytansine derivative) and a sulfo-SPDB linker that joins DM4 to the mirvetuximab antibody. FRα is expressed on the cell surface and has a restricted distribution in normal tissues. However, abnormally high levels of FRα have been detected in serous and endometrioid epithelial ovarian cancer, endometrial adenocarcinoma, and non–small cell lung cancer of the adenocarcinoma subtype. In ovarian cancer patients, its expression is maintained in metastatic foci and recurrent carcinomas. Mirvetuximab soravtansine-gynx binds with high affinity to FRα and is then internalized through antigen-mediated endocytosis. Inside FRα-expressing tumor cells, DM4 is released via proteolytic cleavage. DM4 disrupts the microtubule network within the cell, leading to cell cycle arrest and apoptosis. Since DM4 is electrically neutral and lipophilic, it is able to diffuse across cell membranes and lead to the death of neighboring antigen-negative cells. This "bystander effect" is an important component of mirvetuximab soravtansine-gynx, allowing it to exert a cytotoxic effect even in cells that do not express FRα on their surface.
Mirvetuximab soravtansine is indicated for the treatment of adult patients with folate receptor alpha (FRα) positive, platinum-resistant epithelial ovarian, fallopian tube, or primary peritoneal cancer, who have received one to three prior systemic treatment regimens. Patients are selected for therapy based on an FDA-approved test. This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.
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