Mirvetuximab Soravtansine in Ovarian Cancer Therapy: Expert Opinion on Pharmacological Considerations

Overview

Journal Cancer Chemother Pharmacol

Specialty Oncology

Date 2023 Aug 18

PMID 37594572

Authors

Chukwunonso K Nwabufo

Affiliations

Soon will be listed here.

Abstract

ImmunoGen developed mirvetuximab soravtansine as an antibody-drug conjugate comprising of a humanized anti-folate receptor-α (FRα) monoclonal antibody of IgG1k subtype, a cleavable linker, and a cytotoxic payload, DM4. Mirvetuximab soravtansine was granted accelerated approval by the US FDA on November 14, 2022, for the treatment of adult patients with FRα positive, platinum-resistant epithelial ovarian, fallopian tube or primary peritoneal cancer who have received 1-3 prior systemic treatment regimens. The approval of mirvetuximab soravtansine represents a breakthrough for addressing the unmet medical needs of ovarian cancer, especially for up to 80% of patients who relapse and become resistant to platinum-based chemotherapy, resulting in poor prognosis and limited treatment options. However, it is my impression that addressing several pharmacological factors could improve the safety and efficacy of mirvetuximab soravtansine. This article summarizes the current pharmacological profile of mirvetuximab soravtansine and provides an expert opinion on pharmacological strategies for optimizing its safety and efficacy profile for the treatment of platinum-resistant ovarian cancer.

Citing Articles

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References

Moore K, Martin L, OMalley D, Matulonis U, Konner J, Vergote I . A review of mirvetuximab soravtansine in the treatment of platinum-resistant ovarian cancer. Future Oncol. 2017; 14(2):123-136. DOI: 10.2217/fon-2017-0379. View

Ab O, Whiteman K, Bartle L, Sun X, Singh R, Tavares D . IMGN853, a Folate Receptor-α (FRα)-Targeting Antibody-Drug Conjugate, Exhibits Potent Targeted Antitumor Activity against FRα-Expressing Tumors. Mol Cancer Ther. 2015; 14(7):1605-13. DOI: 10.1158/1535-7163.MCT-14-1095. View

Lambert J . Drug-conjugated antibodies for the treatment of cancer. Br J Clin Pharmacol. 2012; 76(2):248-62. PMC: 3731599. DOI: 10.1111/bcp.12044. View

Widdison W, Wilhelm S, Cavanagh E, Whiteman K, Leece B, Kovtun Y . Semisynthetic maytansine analogues for the targeted treatment of cancer. J Med Chem. 2006; 49(14):4392-408. DOI: 10.1021/jm060319f. View

Oroudjev E, Lopus M, Wilson L, Audette C, Provenzano C, Erickson H . Maytansinoid-antibody conjugates induce mitotic arrest by suppressing microtubule dynamic instability. Mol Cancer Ther. 2010; 9(10):2700-13. PMC: 2976674. DOI: 10.1158/1535-7163.MCT-10-0645. View

Ponte J, Ab O, Lanieri L, Lee J, Coccia J, Bartle L . Mirvetuximab Soravtansine (IMGN853), a Folate Receptor Alpha-Targeting Antibody-Drug Conjugate, Potentiates the Activity of Standard of Care Therapeutics in Ovarian Cancer Models. Neoplasia. 2016; 18(12):775-784. PMC: 5126132. DOI: 10.1016/j.neo.2016.11.002. View

Heo Y . Mirvetuximab Soravtansine: First Approval. Drugs. 2023; 83(3):265-273. DOI: 10.1007/s40265-023-01834-3. View

Martin L, Konner J, Moore K, Seward S, Matulonis U, Perez R . Characterization of folate receptor alpha (FRα) expression in archival tumor and biopsy samples from relapsed epithelial ovarian cancer patients: A phase I expansion study of the FRα-targeting antibody-drug conjugate mirvetuximab soravtansine. Gynecol Oncol. 2017; 147(2):402-407. PMC: 6893864. DOI: 10.1016/j.ygyno.2017.08.015. View

Drewinko B, PATCHEN M, Yang L, Barlogie B . Differential killing efficacy of twenty antitumor drugs on proliferating and nonproliferating human tumor cells. Cancer Res. 1981; 41(6):2328-33. View

10.

Altwerger G, Bonazzoli E, Bellone S, Egawa-Takata T, Menderes G, Pettinella F . and Activity of IMGN853, an Antibody-Drug Conjugate Targeting Folate Receptor Alpha Linked to DM4, in Biologically Aggressive Endometrial Cancers. Mol Cancer Ther. 2018; 17(5):1003-1011. PMC: 5932245. DOI: 10.1158/1535-7163.MCT-17-0930. View

11.

Bargh J, Isidro-Llobet A, Parker J, Spring D . Cleavable linkers in antibody-drug conjugates. Chem Soc Rev. 2019; 48(16):4361-4374. DOI: 10.1039/c8cs00676h. View

12.

Martin-Sabroso C, Lozza I, Torres-Suarez A, Fraguas-Sanchez A . Antibody-Antineoplastic Conjugates in Gynecological Malignancies: Current Status and Future Perspectives. Pharmaceutics. 2021; 13(10). PMC: 8541375. DOI: 10.3390/pharmaceutics13101705. View

13.

Duerr C, Friess W . Antibody-drug conjugates- stability and formulation. Eur J Pharm Biopharm. 2019; 139:168-176. DOI: 10.1016/j.ejpb.2019.03.021. View

14.

Steinfeld R, Grapp M, Kraetzner R, Dreha-Kulaczewski S, Helms G, Dechent P . Folate receptor alpha defect causes cerebral folate transport deficiency: a treatable neurodegenerative disorder associated with disturbed myelin metabolism. Am J Hum Genet. 2009; 85(3):354-63. PMC: 2771535. DOI: 10.1016/j.ajhg.2009.08.005. View

15.

Richardson N, Kasamon Y, Chen H, De Claro R, Ye J, Blumenthal G . FDA Approval Summary: Brentuximab Vedotin in First-Line Treatment of Peripheral T-Cell Lymphoma. Oncologist. 2019; 24(5):e180-e187. PMC: 6516120. DOI: 10.1634/theoncologist.2019-0098. View

16.

Bartsch R . Trastuzumab-deruxtecan: an investigational agent for the treatment of HER2-positive breast cancer. Expert Opin Investig Drugs. 2020; 29(9):901-910. DOI: 10.1080/13543784.2020.1792443. View

17.

Nwabufo C . Relevance of ABC Transporters in Drug Development. Curr Drug Metab. 2022; 23(6):434-446. DOI: 10.2174/1389200223666220621113524. View

18.

Nwabufo C, Aigbogun O . Diagnostic and therapeutic agents that target alpha-synuclein in Parkinson's disease. J Neurol. 2022; 269(11):5762-5786. PMC: 9281355. DOI: 10.1007/s00415-022-11267-9. View

19.

Barbosa M, Vielmetter J, Chu S, Smith D, Jacinto J . Clinical link between MHC class II haplotype and interferon-beta (IFN-beta) immunogenicity. Clin Immunol. 2005; 118(1):42-50. DOI: 10.1016/j.clim.2005.08.017. View

20.

Chirmule N, Jawa V, Meibohm B . Immunogenicity to therapeutic proteins: impact on PK/PD and efficacy. AAPS J. 2012; 14(2):296-302. PMC: 3326159. DOI: 10.1208/s12248-012-9340-y. View