The MIRASOL study (ClinicalTrials.gov identifier: NCT04209855), an international phase 3 randomized clinical trial, found that mirvetuximab soravtansine (Elahere™, ImmunoGen), an antibody-drug conjugate (ADC) and microtubule inhibitor, significantly improved progression-free and overall survival for women with platinum-resistant, advanced high-grade epithelial ovarian, primary peritoneal, or fallopian tube cancers with high folate receptor-alpha (FRɑ) expression.

The results of the study, which was funded by ImmunoGen, were presented at the annual meeting of the American Society of Clinical Oncology (ASCO), held June 2 – 6, 2023, in Chicago, Illinois. [1]

In 2023, there will be an estimated 19,710 new cases and 13,270 deaths in the U.S due to ovarian cancer. If the cancer spreads to distant sites, as is the case with women in this trial, the five-year survival rate is 30%. Over 70% of people annually are diagnosed at this advanced stage.

Folate receptor 1 protein
Folate receptor 1 protein (FOLR1), also known as folate receptor-alpha (FRɑ), is expressed at some level in approximately 90% of ovarian carcinomas and serves as a predictive biomarker for FOLR1-targeted therapy for EOC patients.[2][3]

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To identify patients who are eligible for targeted treatment with mirvetuximab soravtansine, the U.S. Food and Drug Administration (FDA) approval the VENTANA FOLR1 (FOLR1-2.1) RxDx Assay, the first immunohistochemistry (IHC) companion diagnostic test to aid in identifying epithelial ovarian cancer (EOC) patients. The test informs clinicians about the likelihood of potential patient benefit from FOLR1 therapy. [4]

Mirvetuximab soravtansine targets folate receptor-alpha (FRα), which is a member of the folate receptor family that is over-expressed on a variety of epithelial-derived cancer cells. When the drug binds to the receptor, it becomes internalized and leads to cell death.

Study design
Single-agent chemotherapies have shown limited activity and considerable toxicity in patients with platinum-resistant epithelial ovarian cancer. Each successive line of therapy is associated with progressively lower response rates and many patients have difficulty tolerating additional treatments. There have been no new agents specifically indicated for the disease since 2014 when bevacizumab was approved for use with chemotherapy.

In this study, mirvetuximab soravtansine, demonstrated clinically meaningful anti-tumor activity in the single arm SORAYA trial (ClinicalTrials.gov identifier: NCT04296890) reported in January 2023.  This trial is a confirmatory phase 3 study to test the efficacy of the drug in this setting.

Study results
Women who received Mirvetuximab soravtansine not only lived longer when considering all standard chemotherapy medicines together but also each individual drug by itself in this trial. Survival outcomes with mirvetuximab soravtansine were also better, regardless of whether a person received bevacizumab prior to mirvetuximab soravtansine compared to the use of a physician’s choice of chemotherapy.

With a median follow-up of 13.1 months, in the group of 281 women that had previously been treated with bevacizumab, PFS was 36% better and OS was 26% better for women who received mirvetuximab soravtansine vs. the physician’s choice of standard chemotherapy. In the group of 172 women that had not previously received bevacizumab, PFS was 34% better and OS was 49% better for women who received mirvetuximab soravtansine vs. the physician’s choice of standard chemotherapy.

The adverse event profile of mirvetuximab soravtansine was consistent with prior reports — predominantly low-grade ocular and gastrointestinal events. For women taking mirvetuximab soravtansine, 14% remained on the study drug vs. 3% of women receiving physician’s choice of standard chemotherapy.

“Mirvetuximab soravtansine has an FDA accelerated approval so it is hoped that this trial result leads to a quick formal approval.  But more importantly, it opens the door globally for the drug to be available outside the U.S. where accelerated approval isn’t an option. It’s also worth noting that ongoing studies are evaluating moving the drug to being used in earlier stages of the disease,” said Kathleen N. Moore, MD, MS, associate director of clinical research and co-director of the Cancer Therapeutics Program at the Stephenson Cancer Center at the University of Oklahoma in Oklahoma City, OK.

Next Steps
Mirvetuximab soravtansine has now been shown to be most effective when expression of folate receptor-alpha is high. But the investigators found some efficacy when expression levels were moderate or low, which is something they hope to examine more definitively in future studies.  They also hope to incorporate the drug into earlier lines of therapy, including platinum-sensitive, recurrent disease.

Clinical trials
A Study of Mirvetuximab soravtansine vs. Investigator’s Choice of Chemotherapy in Platinum-Resistant, Advanced High-Grade Epithelial Ovarian, Primary Peritoneal, or Fallopian Tube Cancers With High Folate Receptor-Alpha Expression (MIRASOL) – NCT04209855
A Study of Mirvetuximab Soravtansine in Platinum-Resistant, Advanced High-Grade Epithelial Ovarian, Primary Peritoneal, or Fallopian Tube Cancers With High Folate Receptor-Alpha Expression (SORAYA) – NCT04296890

Highlights of prescribing Information
Mirvetuximab soravtansine (Elahere™, ImmunoGen) [Prescribing Information]
Roche. VENTANA FOLR1 (FOLR-2.1) RxDx Assay. [Package Insert]

Reference
[1] Moore KN, Angelergues A, Konecny GE, Banerjee SN, Pignata S, Colombo N, Moroney JW, Cosgrove C. et al.Phase III MIRASOL (GOG 3045/ENGOT-ov55) study: Initial report of mirvetuximab soravtansine vs. investigator’s choice of chemotherapy in platinum-resistant, advanced high-grade epithelial ovarian, primary peritoneal, or fallopian tube cancers with high folate receptor-alpha expression. J Clin Oncol 41, 2023 (suppl 17; abstr LBA5507). DOI 10.1200/JCO.2023.41.17_suppl.LBA5507
[2] Scaranti M, Cojocaru E, Banerjee S, Banerji U. Exploiting the folate receptor α in oncology. Nat Rev Clin Oncol. 2020 Jun;17(6):349-359. doi: 10.1038/s41571-020-0339-5. Epub 2020 Mar 9. PMID: 32152484.
[3] Hilgenbrink AR, Low PS. Folate receptor-mediated drug targeting: from therapeutics to diagnostics. J Pharm Sci. 2005 Oct;94(10):2135-46. doi: 10.1002/jps.20457. PMID: 16136558.
[4] James, R., Admire, B., Sisseron, T et al. 1125P Analytical assessment of a diagnostic immunohistochemical assay for the detection of folate receptor-ɑ in epithelial ovarian cancers. 2021; Annals of Oncology, Volume 32, S921 – S922.

Featured image: 2023 ASCO Annual Meeting – General Views, Chicago, IL – McCormick Place – Photo by © 2023 ASCO/Todd Buchanan. Used with permission.

This article was first published in Onco’Zine.

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