The international phase III MIRASOL randomized clinical trial found that mirvetuximab soravtansine-gynx, an antibody and microtubule inhibitor conjugate, significantly improved progression-free and overall survival for patients with platinum-resistant, advanced high-grade epithelial ovarian, primary peritoneal, or fallopian tube cancers with high folate receptor alpha (FRα) expression. The research was presented by Kathleen N. Moore, MD, MS, at the 2023 ASCO Annual Meeting (Abstract LBA5507).
Kathleen N. Moore, MD, MS
About MIRASOL
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.
The investigational drug used in this trial, mirvetuximab soravtansine, demonstrated clinically meaningful antitumor activity in the single-arm SORAYA trial, reported by Matulonis et al in the Journal of Clinical Oncology in January 2023. The MIRASOL trial is a confirmatory phase III study to test the efficacy of the drug in this setting.
Mirvetuximab soravtansine targets FRα, a member of the folate receptor family that is overexpressed on a variety of epithelial-derived cancer cells. When the drug binds to the receptor, it becomes internalized and leads to cell death.
Key Findings
Patients who received mirvetuximab soravtansine not only lived longer when considering all standard chemotherapy medicines together, but also compared with each drug by itself in this trial. Survival outcomes with mirvetuximab soravtansine were also superior to those with physician’s choice of chemotherapy regardless of whether a person received bevacizumab prior to mirvetuximab soravtansine.
With a median follow-up of 13.1 months, in the group of 281 patients who had previously been treated with bevacizumab, progression-free survival was 36% better and overall survival was 26% better for those who received mirvetuximab soravtansine vs physician’s choice of standard chemotherapy. In the group of 172 patients who had not previously received bevacizumab, progression-free survival was 34% better and overall survival was 49% better for patients who received mirvetuximab soravtansine vs 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 patients taking mirvetuximab soravtansine, 14% remained on the study drug vs 3% of patients receiving physician’s choice of standard chemotherapy.
“Mirvetuximab soravtansine has an FDA [U.S. Food and Drug Administration] 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 United States, 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 Dr. Moore, Associate Director of Clinical Research and Co-Director of the Cancer Therapeutics Program at the Stephenson Cancer Center at the University of Oklahoma.
Next Steps
Mirvetuximab soravtansine has now been shown to be most effective when FRα expression 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.
ASCO Perspective
“Mirvetuximab soravtansine has fewer serious side effects, especially those that can lead to stopping treatment, compared to standard chemotherapies for patients with platinum-resistant ovarian cancer. This, coupled with the overall survival advantage, demonstrates progress and offers hope for these patients,” said ASCO expert Merry Jennifer Markham, MD, FACP, FASCO.
Disclosure: This research was funded by ImmunoGen, Inc. For full disclosures of the study authors, visit coi.asco.org.
