FDA Gives Nod to Mirvetuximab Soravtansine

The FDA has granted accelerated approval to mirvetuximab soravtansine (Elahere; ImmunoGen) for patients who have received one to three prior systemic treatments for folate receptor alpha (FRα)–positive, platinum-resistant epithelial ovarian, fallopian tube, or primary peritoneal cancer. The approval of this FRα-directed antibody and microtubule inhibitor conjugate provides another therapy for patients who have limited treatment options.

“Effective treatments for platinum-resistant ovarian cancer continue to be an unmet need. The development of mirvetuximab adds another option for us to care for these patients,” says Paul DiSilvestro, MD, of the Women & Infants Hospital of Rhode Island in Providence. A cell-surface protein, FRα is overexpressed in about 80% of epithelial ovarian and other cancers. An antibody–drug conjugate (ADC), mirvetuximab soravtansine consists of an FRα-binding antibody, a cleavable linker, and the microtubule-targeting agent DM4. After antigen binding, the cell internalizes the ADC and DM4 is released, causing cell-cycle arrest and apoptosis.

The accelerated approval was based on the results of the phase III SORAYA trial (Study 0417), a single-arm study involving 106 women with platinum-resistant epithelial ovarian, fallopian tube, or primary peritoneal cancer with high FRα expression, defined as occurring on at least 75% of tumor cells. Participants had received one to three treatment regimens, and all of them had taken bevacizumab. Patients received mirvetuximab soravtansine intravenously every 3 weeks until disease progression or unacceptable toxicity. The overall response rate was 31.7%, with five complete responses and 29 partial ones; the median duration of response was 6.9 months.

To detect the FRα protein and determine which patients could respond to the drug, the FDA also approved the VENTANA FOLR1 (FOLR-2.1) RxDx Assay (Roche) companion diagnostic device.

“This test is currently offered by several companies and will be established in clinical laboratories. The label for this drug is truly biomarker driven so it has to be an ovarian [or fallopian tube and primary peritoneal] cancer that is FRα positive,” says Oliver Dorigo, MD, PhD, of Stanford Women's Cancer Center in Palo Alto, CA.

This drug comes with a boxed warning for ocular toxicity because some of the most common adverse events in the SORAYA study included vision impairment, keratopathy, and dry eye. The agency recommends monitoring eyes through the slit lamp microscope with a bright light exam or the Snellen letter chart test and administering prophylactic artificial tears and ophthalmic topical steroids.

“Financial toxicity must be considered as well, so working closely with patients and insurers will be critical to making certain we can deliver this treatment without creating further burdens for our patients,” says DiSilvestro. ImmunoGen set the list price for a vial of mirvetuximab soravtansine at $6,220, with three to four vials needed for each treatment cycle—bringing the cost to $18,660 to $24,880 per cycle.

Full approval is contingent upon additional research confirming mirvetuximab soravtansine's safety and efficacy in treating FRα-positive, platinum-resistant epithelial ovarian, primary peritoneal, and fallopian tube cancers. Researchers are enrolling 453 patients in the phase III MIRASOL trial, which is comparing mirvetuximab soravtansine with physician's choice of a standard chemotherapy—paclitaxel, pegylated liposomal doxorubicin, or topotecan. Two hundred and eight trial sites across four continents will participate in the study. Initial results are expected in 2023, with an estimated completion date of April 2024. –Aaron Tallent

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