Mirvetuximab soravtansine is a targeted therapy for ovarian cancer. This medication treats platinum-resistant epithelial ovarian, fallopian tube, and primary peritoneal cancers. It offers a precise approach by focusing on specific cancer cell characteristics, aiming to reduce harm to healthy tissues.
Targeting Ovarian Cancer Cells
Mirvetuximab soravtansine functions as an antibody-drug conjugate (ADC), combining an antibody’s precise targeting ability with a potent cancer-killing agent. The antibody component binds to folate receptor alpha (FRα), a protein often found in high amounts on ovarian cancer cells. This selective binding allows the medication to differentiate between cancerous and healthy cells, guiding its therapeutic payload directly to the tumor.
Once mirvetuximab attaches to FRα, the cell internalizes the complex through receptor-mediated endocytosis. Inside the cell, in the lysosome, a linker connecting the antibody to the cytotoxic agent is cleaved. This releases the active drug, DM4, a maytansinoid. DM4 interferes with tubulin, a protein essential for cell division, leading to the cancer cell’s death.
Patient Eligibility for Mirvetuximab
Mirvetuximab soravtansine is approved for adult patients with FRα-positive, platinum-resistant epithelial ovarian, fallopian tube, or primary peritoneal cancer. These patients must have previously undergone one to three systemic treatment regimens. “Platinum-resistant” means the cancer progressed during platinum-based chemotherapy or within six months of completing it.
To determine eligibility, patients undergo a test to confirm FRα presence and level on their tumor cells. The VENTANA FOLR1 (FOLR1-2.1) RxDx Assay identifies patients whose tumors express high levels of FRα, defined as at least 75% of viable tumor cells showing moderate to strong staining.
Administering Mirvetuximab and Potential Side Effects
Mirvetuximab soravtansine is administered as an intravenous (IV) infusion, typically once every three weeks, as part of a 21-day cycle. The recommended dosage is 6 mg per kilogram of adjusted ideal body weight, continuing until disease progression or unacceptable side effects. Before each infusion, patients receive premedications like corticosteroids, antihistamines, and antiemetics to prevent infusion-related reactions and manage nausea and vomiting.
Patients may experience side effects, with ocular issues being common. These include blurred vision, dry eyes, light sensitivity, and changes to the cornea (keratopathy). To manage these, patients are often prescribed steroid and lubricating eye drops and are monitored by an eye care professional. Other common side effects include nausea, fatigue, diarrhea, and peripheral neuropathy (numbness or tingling in hands or feet). These side effects are monitored by the healthcare team, and dose adjustments or supportive care can be implemented.
Observed Treatment Outcomes
Clinical studies demonstrate mirvetuximab soravtansine’s effectiveness. In the SORAYA trial, a single-arm Phase 2 study, mirvetuximab achieved an objective response rate (ORR) of 32.4% in patients with FRα-high, platinum-resistant ovarian cancer. The median duration of response (DOR) was 6.9 months.
The confirmatory Phase 3 MIRASOL trial compared mirvetuximab to conventional chemotherapy in a similar patient population. This trial showed improved progression-free survival (PFS) for patients receiving mirvetuximab, with a median PFS of 5.62 months compared to 3.98 months for those on chemotherapy. Overall survival was also longer in the mirvetuximab group, with a median of 16.46 months versus 12.75 months for chemotherapy, representing a 32% reduction in the risk of death.