The European Medicines Agency’s (EMA) Committee for Medicinal Products for Human Use (CHMP) has issued a positive opinion recommending marketing authorization for mirvetuximab soravtansine (Elahere; AbbVie) for the treatment of adult patients with folate receptor alpha–positive (FRα+), platinum-resistant, high-grade serous epithelial ovarian, primary peritoneal, or fallopian tube cancer who have received one to three prior treatment regimens. This decision marks a significant step toward providing a new treatment option for patients with limited alternatives.
The recommendation is based on data from the phase 3 MIRASOL trial (NCT04209855), a randomized, open-label study comparing mirvetuximab soravtansine to investigator's choice of single-agent chemotherapy (paclitaxel, pegylated liposomal doxorubicin, or topotecan). The trial enrolled 453 patients with platinum-resistant, high-grade serous ovarian cancer whose tumors expressed high levels of FRα, defined as expression on at least 75% of cells with at least 2+ staining intensity.
Efficacy and Safety Data from MIRASOL
Results from the MIRASOL trial demonstrated a statistically significant improvement in progression-free survival (PFS) for patients treated with mirvetuximab soravtansine. The median investigator-assessed PFS was 5.6 months (95% CI, 4.3-5.9) in the mirvetuximab soravtansine arm compared to 4.0 months (95% CI, 2.9-4.5) in the chemotherapy arm (HR, 0.65; 95% CI, 0.52-0.81; P < .0001). At 12 months, the restricted mean PFS was 6.13 months (95% CI, 5.62-6.64) with mirvetuximab soravtansine vs 4.72 months (95% CI, 4.21-5.23) with chemotherapy.
The objective response rate (ORR) was also significantly higher in the mirvetuximab soravtansine arm, at 42% (95% CI, 36-49), including a complete response rate of 5% and a partial response rate of 37%. In the chemotherapy arm, the ORR was 16% (95% CI, 12-22; P < .0001), with all responses being partial responses.
Overall survival (OS) data also favored mirvetuximab soravtansine, with a median OS of 16.5 months (95% CI, 14.5-24.6) compared to 12.7 months (95% CI, 10.9-14.4) with chemotherapy (HR, 0.67; 95% CI, 0.50-0.88; P = .0046). The median duration of response was 6.77 months (95% CI, 5.62-8.31) in the mirvetuximab soravtansine arm versus 4.47 months (95% CI, 4.17-5.82) in the chemotherapy arm (HR, 0.62; 95% CI, 0.40-0.97).
Regarding safety, the most common any-grade adverse events (AEs) in the mirvetuximab soravtansine arm were blurred vision (40.8%), keratopathy (32.1%), abdominal pain (30.3%), and fatigue (30.3%). Grade 3 or higher AEs occurred in 41.7% of patients in the mirvetuximab soravtansine arm versus 54.1% in the chemotherapy arm. Serious AEs occurred in 23.9% and 32.9% of patients in the respective arms. Discontinuation of treatment due to AEs occurred in 9.2% of patients in the mirvetuximab soravtansine arm.
Expert Commentary
Roopal Thakkar, MD, executive vice president of research and development and chief scientific officer of AbbVie, stated, “Following many years of development by the ImmunoGen team that is now part of AbbVie, we are hopeful to make mirvetuximab soravtansine available to eligible patients with ovarian cancer in the European Union. This positive opinion recognizes the unmet need for certain patients with platinum-resistant ovarian cancer.”
Next Steps
The CHMP’s recommendation will now be reviewed by the European Commission (EC), with a final decision expected later in 2024. If approved, mirvetuximab soravtansine will provide a new treatment option for patients with FRα+ platinum-resistant ovarian cancer in the European Union.
FDA Approval and Ongoing Research
Mirvetuximab soravtansine received full approval from the FDA in March 2024 for a similar indication, based on the MIRASOL trial findings. The drug is also being evaluated in multiple studies, both as monotherapy and in combination with other agents, for ovarian cancer, which is likely to expand its use in earlier lines of therapy and additional patient populations.
Impact on Ovarian Cancer Treatment
Ovarian cancer remains a significant cause of mortality among gynecological cancers. Most patients are diagnosed with late-stage disease and, while initially responsive to platinum-based chemotherapy, often develop resistance, necessitating alternative treatments. Mirvetuximab soravtansine, a first-in-class antibody-drug conjugate (ADC), offers a targeted approach by combining a folate receptor-alpha binding antibody with a potent tubulin inhibitor, DM4, designed to kill targeted cancer cells.
