On November 14, the U.S. Food and Drug Administration (FDA) granted accelerated approval to mirvetuximab soravtansine-gynx (Elahere) for adult patients with folate receptor alpha (FRα)-positive, platinum-resistant epithelial ovarian, fallopian tube, or primary peritoneal cancer, who have received one to three prior systemic treatment regimens. Mirvetuximab soravtansine is an FRα-directed antibody and microtubule inhibitor–conjugate. Patients are selected for therapy based on an FDA-approved test. The FDA also approved the VENTANA FOLR1 (FOLR-2.1) RxDx Assay as a companion diagnostic to select patients for the above indication.
Efficacy was evaluated in the SORAYA study, also known as Study 0417 (ClinicalTrials.gov identifier: NCT04296890), a single-arm trial of 106 patients with FRα-positive, platinum-resistant epithelial ovarian, fallopian tube, or primary peritoneal cancer. Patients were permitted to receive up to three prior lines of systemic therapy; all patients were required to have received bevacizumab. The trial enrolled patients whose tumors were positive for FRα expression as determined by the above assay. Patients were excluded if they had corneal disorders, ocular conditions requiring ongoing treatment, grade > 1 peripheral neuropathy, or noninfectious interstitial lung disease.
Patients received mirvetuximab soravtansine at 6 mg/kg (based on adjusted ideal body weight) as an intravenous infusion every 3 weeks until disease progression or unacceptable toxicity. Tumor response assessments occurred every 6 weeks for the first 36 weeks and every 12 weeks thereafter.
The main efficacy outcome measures were investigator-assessed overall response rate and duration of response evaluated according to Response Evaluation Criteria in Solid Tumors version 1.1. In the efficacy-evaluable population of patients who had platinum-resistant, measurable disease and received at least one dose of therapy (n = 104), the confirmed overall response rate was 31.7% (95% confidence interval [CI] = 22.9%–41.6%) and median duration of response was 6.9 months (95% CI = 5.6–9.7 months).
The most common (≥ 20%) adverse reactions, including laboratory abnormalities, were vision impairment, fatigue, increased aspartate aminotransferase, nausea, increased alanine aminotransferase, keratopathy, abdominal pain, decreased lymphocytes, peripheral neuropathy, diarrhea, decreased albumin, constipation, increased alkaline phosphatase, dry eye, decreased magnesium, decreased leukocytes, decreased neutrophils, and decreased hemoglobin. Product labeling includes a boxed warning for ocular toxicity.
“This accelerated approval of mirvetuximab soravtansine for [FRα-positive, platinum-resistant epithelial ovarian, fallopian tube, or primary peritoneal cancer] is incredibly meaningful for patients who have this cancer,” Ursula A. Matulonis, MD, Chief of the Division of Gynecologic Oncology and the Brock-Wilson Family Chair at Dana-Farber Cancer Institute and co-leader of the SORAYA study. “There have been no approved therapies for platinum resistant ovarian cancer since 2014, so [this] action by the FDA is a very significant milestone.”
The recommended mirvetuximab soravtansine dose is 6 mg/kg adjusted ideal body weight administered once every 3 weeks (21-day cycle) as an intravenous infusion until disease progression or unacceptable toxicity.
This application was granted Priority Review.