Updated MIRASOL Data Support Mirvetuximab Soravtansine as SOC for FRα+ Platinum-Resistant Ovarian Cancer

Mirvetuximab soravtansine-gynx (Elahere) continued to showcase superior overall survival (OS) and maintained other clinical benefits over investigator’s choice of chemotherapy (ICC) in patients with folate receptor α (FRα)–positive, platinum-resistant ovarian cancer, according to the final analysis of the phase 3 MIRASOL trial (NCT04209855) presented during the 2025 SGO Annual Meeting on Women’s Cancer.1

At a median follow-up of 30.5 months, the median OS with mirvetuximab (n = 227) was 16.85 months (95% CI, 14.36-19.78) vs 13.34 months (95% CI, 11.37-15.15) with ICC (n = 226), translating to a 32% reduction in the risk of death with the antibody-drug conjugate (ADC; HR, 0.68; 95% CI, 0.54-0.84; P = .0004). Moreover, a trend of improved OS for the ADC vs chemotherapy was observed across key subgroups, irrespective of prior exposure to bevacizumab (Avastin), PARP inhibitor maintenance, number of prior lines of therapy, and type of ICC.

“Mirvetuximab is the first novel treatment to show statistically significant and clinically meaningful OS benefits over ICC in platinum-resistant ovarian cancer and [the agent] continued to show a superior OS compared to chemotherapy at this final analysis, after a follow-up time of 30.5 months,” Toon Van Gorp, MD, PhD, of University Hospital Leuven Kefir Cancer Institute and BGOG, in Leuven, Belgium, said in an oral presentation of the data. “The same can also be said about progression-free survival [PFS], objective response rate [ORR], and also duration of response [DOR]…I think it’s fair to say that mirvetuximab should be the standard of care for patients with FRα-positive, platinum-resistant ovarian cancer.”

Diving Into MIRASOL: Design, Treatment, Objectives

The global, randomized, open-label, phase 3 study enrolled patients with platinum-resistant ovarian cancer with FRα positivity by immunohistochemistry, and high-grade serous histology. Patients had received 1 to 3 prior lines of therapy, with previous exposure to bevacizumab or PARP inhibitors permitted.

Participants were randomized 1:1 to receive mirvetuximab soravtansine at an intravenous dose of 6 mg/kg based on adjusted ideal body weight every 3 weeks or ICC, which could have included paclitaxel, pegylated liposomal doxorubicin (PLD), or topotecan. Treatment continued until disease progression or intolerable toxicity. Patients were stratified based on ICC (paclitaxel vs PLD vs topotecan) and prior lines of therapy (1 vs 2 vs 3). Investigator-assessed PFS served as the primary end point and key secondary end points included investigator-assessed ORR, OS, and patient-reported outcomes. Investigators also examined safety and tolerability, DOR, CA-125 response, and second PFS (PFS2).

Data from the primary analysis of the study showed that at a median follow-up of 13.1 months, the ADC significantly improved PFS, ORR, and OS over ICC.2,3 Specifically, the median PFS with mirvetuximab was 5.62 months (95% CI, 4.34-5.95) vs 3.98 months (95% CI, 2.86-4.47) with ICC (P < .001). The ADC elicited an ORR of 42.3% vs 15.9% with ICC (OR, 3.81; 95% CI, 2.44-5.94; P < .001). Lastly, the median OS was 16.46 months (95% CI, 14.46-24.57) with mirvetuximab vs 12.75 months (95% CI, 10.91-14.36) with ICC (HR, 0.67; 95% CI, 0.50-0.89; P = .005).

Mirvetuximab won accelerated approval from the FDA in November 2022 for use in adult patients with FRα-positive, platinum-resistant epithelial ovarian, fallopian tube, or primary peritoneal cancer, who have previously received 1 to 3 systemic treatment regimens based on data from the phase 3 SORAYA trial (NCT04296890).4 The ADC won full approval in March 2024 for this indication based on earlier data from MIRASOL, the confirmatory trial.5

Additional Long-Term Efficacy Findings

At the time of the final analysis, the median PFS with mirvetuximab soravtansine was 5.59 months (95% CI, 4.34-5.88) vs 3.98 months (95% CI, 2.86-4.47) with ICC, translating to a 37% reduction in the risk of disease progression or death (HR, 0.63; 95% CI, 0.51-0.79; P < .0001).

Moreover, the ADC elicited an ORR of 41.9% (95% CI, 35.4%-48.6%) vs 15.9% (95% CI, 11.4%-21.4%) with ICC (OR, 3.75; 95% CI, 2.4-5.85). In the mirvetuximab arm, 5.7% of patients experienced complete responses and 36.1% experienced partial responses; 38.3% had stable disease, 13.7% experienced disease progression, and 6.2% were not evaluable. The median DOR with the ADC was 6.93 months (95% CI, 5.78-8.84) vs 4.44 months (95% CI, 4.17-5.75) with ICC. The median PFS2 in the respective arms was 11.01 months (95% CI, 9.30-12.02) and 7.59 months (95% CI, 6.60-8.84; HR, 0.59; 95% CI, 0.480-0.728).

Safety Spotlight

“Mirvetuximab continues to have less grade 3 or more treatment-emergent adverse effects [TEAEs], less serious adverse effects [AEs], and also less AEs leading to discontinuation,” Van Gorp said. “Patients that needed to discontinue the treatment due to AEs was almost twice as high in the ICC arm.”

Any-grade TEAEs occurred in 97% of those in the mirvetuximab arm (n = 218) vs 94% of those in the ICC arm (n = 207); these effects were grade 3 or higher for 44% and 55% of patients, respectively. Any serious TEAEs occurred in 25% and 33% of patients, respectively, and these effects were grade 3 or higher for 22% and 29% of patients. TEAEs led to dose delay or hold for 56% of those in the ADC arm vs 54% of those in the ICC arm; they led to dose reductions for 35% and 24% of patients, respectively. Moreover, 11% of patients in the mirvetuximab arm experienced TEAEs that led to discontinuation vs 15% of those in the ICC arm; grade 3 or higher TEAEs led to discontinuation in 6% and 11% of patients. Four patients in the mirvetuximab arm experienced TEAEs that led to death vs 5 patients in the ICC arm.

The most common all grade TEAEs reported with mirvetuximab were blurred vision (43%), keratopathy (33%), dry eye (29%), diarrhea (29%), nausea (27%), peripheral neuropathy (22%), neutropenia (11%), anemia (10%), thrombocytopenia (8%), stomatitis (4%), and alopecia (1%).

“Mirvetuximab is causing less hematological AEs. We do see some peripheral neuropathy, but it’s less severe compared to paclitaxel; it’s mainly grade 1 and 2,” Van Gorp noted. “We hardly see any alopecia, which is important for our patients. We do see some diarrhea and nausea, at the same level as what we see with ICC. Of course, a typical AE for mirvetuximab are the ocular AEs, but there is a mitigation strategy, and if necessary, there can be dose modifications.”

Ongoing studies are further examining mirvetuximab soravtansine in combination with other therapies and in earlier lines, Van Gorp concluded.

Disclosures: Van Gorp disclosed receipt of grants/research support from AstraZeneca, Roche, and Amgen; receipt of honoraria or consultation fees from AbbVie, AstraZeneca, BioNTech, Cancer Communications and Consultancy Ltd, Daiichi Sankyo, Eisai, GSK, ImmunoGen, Incyte, Karyopharm, MSD/Merck, OncXerna Therapeutics, Seagen, Tubulis, and Zentalis. He disclosed participating in a company-sponsored speakers’ bureau at AbbVie, AstraZeneca, Eisai, GSK, ImmunoGen, and MSD, and receiving travel expenses, accommodations, and expenses from AstraZeneca, GSK, ImmunoGen, MSK, PharmaMar, and Roche.

References

1. Van Gorp T, Angelergues A, Konecny G, et al. Final overall survival analysis among patients with FRα-positive, platinum-resistant ovarian cancer (PROC) treated with mirvetuximab soravtansine (MIRV) vs investigator’s choice chemotherapy (ICC) in the phase 3 MIRASOL (GOG 3045/ENGOT-ov55) study. Presented at: 2025 SGO Annual Meeting on Women’s Cancer; March 14-17, 2025; Seattle, WA. Abstract 939696.
2. Moore KN, Angelergues A, Konecny GE, et al. Mirvetuximab soravtansine in FRα-positive, platinum-resistant ovarian cancer. N Engl J Med. 2023;389(23):2162-2174. doi:10.1056/NEJMoa2309169
3. Moore KN, Angelergues A, Konecny GE, 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. 2023;41(suppl 17):LBA5507. doi:10.1200/JCO.2023.41.17_suppl.LBA5507
4. 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 March 16, 2025. https://news.abbvie.com/2022-11-14-ImmunoGen-Announces-FDA-Accelerated-Approval-of-ELAHERE-TM-mirvetuximab-soravtansine-gynx-for-the-Treatment-of-Platinum-Resistant-Ovarian-Cancer
5. FDA approves mirvetuximab soravtansine-gynx for FRα positive, platinum-resistant epithelial ovarian, fallopian tube, or primary peritoneal cancer. FDA. March 22, 2024. Accessed March 16, 2025. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-mirvetuximab-soravtansine-gynx-fra-positive-platinum-resistant-epithelial-ovarian