Mirvetuximab Soravtansine Improves PFS, OS in FRα+ Platinum-Resistant Ovarian Cancer

Mirvetuximab soravtansine-gynx (Elahere) led to a clinically meaningful and statistically significant improvement in progression-free survival (PFS), overall survival (OS), and objective response rate (ORR) vs single-agent chemotherapy in patients with platinum-resistant ovarian cancer whose tumors express high levels of folate receptor alpha (FRα), according to topline findings from the phase 3 MIRASOL trial (NCT04209855).¹

Results indicated that the investigator-assessed median PFS with mirvetuximab soravtansine was 5.62 months vs 3.98 months with chemotherapy (HR, 0.65; P < .0001). At a median follow-up of 13.1 months, the median OS with mirvetuximab soravtansine and chemotherapy was 16.46 months and 12.75 months, respectively (HR, 0.67; P = .0046).

Treatment with the antibody-drug conjugate (ADC) also produced an ORR of 42.3% by investigator assessment, which included 12 complete responses (CRs), compared with an ORR of 15.9% and no CRs with chemotherapy. Investigator-assessed PFS and ORR were concordant with results by blinded independent central review.

ImmunoGen plans to submit a marketing authorization application to the European Medicines Agency and a supplemental biologics license application to the FDA in the second half of this year based on findings from MIRASOL.

“I believe the data from the confirmatory MIRASOL trial are practice changing. They demonstrate Elahere’s superiority to chemotherapy based on all efficacy end points, in particular OS, and build on the clinical benefit of Elahere previously reported in the SORAYA trial [NCT04296890],” Kathleen Moore, MD, MS, associate director of Clinical Research and director of the Oklahoma TSET/Sarah Cannon Phase I Program, professor of the Section of Gynecologic Oncology at The University of Oklahoma, in Norman Oklahoma, and MIRASOL principal investigator, stated in a news release.

In November 2022, the FDA granted an accelerated approval to mirvetuximab soravtansine for the treatment of adult patients with FRα-positive, platinum-resistant epithelial ovarian, fallopian tube, or primary peritoneal cancer who have received 1 to 3 prior lines of systemic therapy based on ORR and duration of response data from the phase 3 SORAYA trial.² Specifically, the ADC induced an ORR of 37.1% (95% CI, 22.9%-41.6%) per investigator assessment, which comprised a CR and partial response rate of 4.8% and 26.9%, respectively. The median duration of response with mirvetuximab soravtansine was 6.9 months (95% CI, 5.6-9.7).

“Last year’s accelerated approval of Elahere was a paradigm-shifting development in the treatment landscape for this disease and I am confident that, with the MIRASOL data, Elahere has the potential to become the new standard of care for patients with FRα-positive, platinum-resistant ovarian cancer,” Moore added. “FRα status is a must know for all [patients with] ovarian cancer and, for those with platinum-resistant disease who test positive, I believe Elahere should be their first treatment option.”

The subsequent MIRASOL trial compared mirvetuximab soravtansine with investigator’s choice of weekly paclitaxel, pegylated liposomal doxorubicin, or topotecan. To be eligible for enrollment, patients had to have platinum-resistant ovarian cancer with high levels of FRα expression, using the Ventana FOLR1 assay, that has been pretreated with up to three prior lines of therapy.

The primary end point of the trial is investigator-assessed PFS. Key secondary end points include ORR and OS.

At the data cutoff date of March 6, 2023, a total of 453 patients were enrolled to the trial. Notably, 14% of patients received 1 prior line of therapy, 39% received 2 prior lines, and 47% received 3 prior lines. Specifically, more than half of patients (62%) previously received bevacizumab (Avastin) and 55% received a prior PARP inhibitor.

At the time of data cutoff, 14% of patients in the mirvetuximab soravtansine arm were still receiving treatment vs 3% of those in the chemotherapy arm.

“We are elated with the positive top-line results from MIRASOL. We believe the impressive efficacy data and consistent safety data reinforce Elahere’s benefit for patients with platinum-resistant ovarian cancer,” Anna Berkenblit, MD, senior vice president and chief medical officer of ImmunoGen, added in the press release. “Importantly, Elahere is the first drug to show an OS benefit in this patient population. These results are remarkable, and we extend our appreciation to all the patients and physicians who participated in MIRASOL. We look forward to presenting full data from the trial at a medical meeting later this year.”

The primary toxicities associated with the ADC included low-grade ocular and gastrointestinal events. No new safety signals were identified. Notably, mirvetuximab soravtansine was associated with lower rates of grade 3 or greater treatment-emergent adverse effects (TEAEs; 42% vs 54%), serious AEs (24% vs 33%), and TEAEs leading to study discontinuation (9% vs 16%) compared with chemotherapy, respectively.

References

1. Elahere demonstrates overall survival benefit in the phase 3 MIRASOL trial in patients with FRα-positive platinum-resistant ovarian cancer. News release. ImmunoGen Inc. May 3, 2023. Accessed May 3, 2023. https://investor.immunogen.com/news-releases/news-release-details/elaherer-demonstrates-overall-survival-benefit-phase-3-mirasol
2. ImmunoGen announces FDA accelerated approval of Elahere (mirvetuximab soravtansine-gynx) for the treatment of platinum-resistant ovarian cancer. News release. ImmunoGen Inc. November 14, 2022. Accessed May 3, 2023. https://investor.immunogen.com/news-releases/news-release-details/immunogen-announces-fda-accelerated-approval-elaheretm