FDA Grants Accelerated Approval to Mirvetuximab Soravtansine-Gynx for FR Alpha–Positive, Platinum-Resistant Epithelial Ovarian, Fallopian Tube, or Peritoneal Cancer
On November 14, 2022, the U.S. Food and Drug Administration (FDA) granted accelerated approval (https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-accelerated-approval-mirvetuximab-soravtansine-gynx-fra-positive-platinum-resistant) to mirvetuximab soravtansine-gynx (Elahere®) for adult patients with folate receptor (FR) alpha–positive, platinum-resistant epithelial ovarian, fallopian tube, or primary peritoneal cancer, as detected with an FDA-approved test, who received one to three prior systemic treatment regimens. Mirvetuximab soravtansine-gynx is a FR alpha–directed antibody and microtubule inhibitor conjugate. FDA also approved the VENTANA FOLR1 (FOLR-2.1) RxDx Assay (Ventana Medical Systems, Inc.) as a companion diagnostic device to identify patients for the indication.
Efficacy was evaluated in study 0417 (NCT04296890), a single-arm trial of 106 patients with FR alpha–positive, platinum-resistant epithelial ovarian, fallopian tube, or primary peritoneal cancer. Patients received up to three prior lines of systemic therapy, at least one of which that included bevacizumab, and their tumors were positive for FR alpha expression as determined by the companion assay. Patients were excluded if they had corneal disorders, ocular conditions requiring ongoing treatment, greater than grade 1 peripheral neuropathy, or noninfectious interstitial lung disease.
Patients received mirvetuximab soravtansine-gynx 6 mg/kg based on adjusted ideal body weight via IV every three weeks until they experienced disease progression or unacceptable toxicity. Tumor response was assessed every six weeks for the first 36 weeks and every 12 weeks thereafter.
The main efficacy outcome measures were investigator-assessed overall response rate (ORR) and duration of response (DOR) evaluated according to RECIST version 1.1. In the efficacy evaluable population of patients who had platinum-resistant, measurable disease and received at least one dose (104 patients), the confirmed ORR was 31.7% (95% CI = 22.9, 41.6) and median DOR was 6.9 months (95% CI = 5.6, 9.7).
The most common adverse reactions reported in at least 20% of patients treated with mirvetuximab soravtansine-gynx were laboratory abnormalities, 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. The package insert has a boxed warning for ocular toxicity.
The recommended mirvetuximab soravtansine-gynx dose is 6 mg/kg based on adjusted ideal body weight administered once every three weeks (21-day cycle) via IV until patients experience disease progression or unacceptable toxicity.
The application was granted priority review. A description of FDA expedited programs is in the Guidance for Industry: Expedited Programs for Serious Conditions–Drugs and Biologics (https://www.fda.gov/regulatory-information/search-fda-guidance-documents/expedited-programs-serious-conditions-drugs-and-biologics).
Healthcare professionals should report all serious adverse events suspected to be associated with the use of any medicine and device to FDA’s MedWatch Reporting System (https://www.accessdata.fda.gov/scripts/medwatch/index.cfm) or by calling 800-FDA-1088.
For assistance with single-patient investigational new drug applications, contact OCE’s Project Facilitate (https://www.fda.gov/about-fda/oncology-center-excellence/project-facilitate) at 240-402-0004 or email OncProjectFacilitate@fda.hhs.gov (mailto:OncProjectFacilitate@fda.hhs.gov).