Of 106 women in the pivotal trial, 31.7% saw their tumors respond to Elahere. Five had a complete response. The median response lasted 6.9 months.
Those numbers were enough for the FDA to grant accelerated approval to the drug, known generically as mirvetuximab soravtansine-gynx and made by ImmunoGen, which announced the decision on Nov. 14, 2022. The approval covers adults with folate receptor alpha (FRα)-positive, platinum-resistant epithelial ovarian, fallopian tube or primary peritoneal cancer who have had one to three prior systemic treatment regimens. It is the first antibody drug conjugate approved for platinum-resistant disease, and it can be used whether or not a patient previously received Avastin.
How the drug works
Elahere pairs an antibody that binds folate receptor alpha with a cleavable linker and DM4, a maytansinoid payload that blocks tubulin and is meant to kill the cancer cell it reaches. Patients receive 6 mg/kg, adjusted for ideal body weight, intravenously once every three weeks.
Only some tumors qualify. Roughly 35-40% of ovarian cancer patients have high FRα levels. The FDA approved a companion test at the same time, Roche’s VENTANA FOLR1 (FOLR1-2.1) RxDx Assay, to identify them. Testing works on fresh or archived tissue, and ImmunoGen said newly diagnosed patients can be tested at diagnosis.
The trial and the warnings
The SORAYA study was a single-arm trial. Its 106 patients had platinum-resistant disease with high FRα expression, and all had been treated with bevacizumab. The safety review pooled data from three studies covering 464 patients.
The label carries a boxed warning for ocular toxicity. Eye problems occurred in 61% of patients, and 9% had Grade 3 reactions. Visual impairment affected 49%, keratopathy 36%, dry eye 26%, cataract 15%, photophobia 13% and eye pain 12%. The label calls for an eye exam before treatment starts and at every other cycle for the first eight cycles, along with artificial tears and topical steroid drops. Pneumonitis occurred in 10% of patients; one patient died of respiratory failure in the setting of pneumonitis and lung metastases.
Other common adverse events included fatigue, nausea, abdominal pain, peripheral neuropathy, diarrhea, constipation and decreased lymphocytes, along with raised liver enzymes.
What the doctors said
Ursula Matulonis, chief of gynecologic oncology at Dana-Farber Cancer Institute and a co-principal investigator of SORAYA, said the approval matters for a group with “limited treatment options and poor outcomes.” She cited the drug’s “impressive anti-tumor activity, durability of response, and overall tolerability.”
Anna Berkenblit, ImmunoGen’s chief medical officer, noted that the FDA had approved no new therapy for this indication since 2014. “Platinum-resistant ovarian cancer is a notoriously challenging disease to treat,” she said.
Ovarian cancer is the leading cause of death from gynecological cancers in the U.S. About 20,000 patients are diagnosed each year, and 13,000 die. Most are diagnosed late, and most eventually develop platinum resistance.
Because the approval is accelerated, continued approval may depend on a confirmatory trial. That trial, MIRASOL, is fully enrolled, with top-line data expected in early 2023.
Sources
- FDA Approves Mirvetuximab Soravtansine-gynx for Platinum-Resistant Ovarian Cancer | AJMC
- ImmunoGen Announces FDA Accelerated Approval of ELAHERE™ (mirvetuximab soravtansine-gynx) for the Treatment of Platinum-Resistant Ovarian Cancer
Sources
- FDA Approves Mirvetuximab Soravtansine-gynx for… | AJMC
- ImmunoGen Announces FDA Accelerated Approval of ELAHERE…
