Mirvetuximab soravtansine for platinum-resistant epithelial ovarian cancer

Mirvetuximab soravtansine (mirvetuximab) is an antibody drug conjugate (ADC) comprised of a humanized folate receptor alpha (FRα)-binding monoclonal antibody attached via a cleavable linker to the cytotoxic maytansinoid molecule, DM4. FRα is expressed in several epithelial cancers, including high grade serous ovarian cancer (HGSOC). Mirvetuximab received accelerated approval by the United States Food and Drug Administration (FDA) in November 2022 based on the results of the SORAYA trial, which tested mirvetuximab for the treatment of patients with recurrent platinum resistant HGSOC with high FRα expression and showed an overall response rate (ORR) of 32.4% and a median duration of response of 6.9 months. Mirvetuximab toxicities included low grade ocular and gastrointestinal toxicities. The National Comprehensive Cancer Network (NCCN) ovarian cancer 2023 guidelines adopted mirvetuximab as 2A, and mirvetuximab combined with bevacizumab as 2B, recommendations.

This manuscript will review the preclinical and clinical development of mirvetuximab, the toxicities associated with mirvetuximab and mitigation strategies, and future applications of mirvetuximab.

Mirvetuximab represents the first biomarker-directed therapy with an indication specifically for the treatment of PROC. The efficacy and favorable safety profile support further development of mirvetuximab and mirvetuximab combinations in platinum sensitive and newly diagnosed ovarian cancer.