Results from the phase 3 SORAYA trial supported the acceptance of a biologics license application for mirvetuximab soravtansine under priority review by the FDA for patients with folate receptor α–high platinum-resistant ovarian cancer.
The FDA has accepted a biologics license application for mirvetuximab soravtansine under priority review for patients with folate receptor α (FRα)–high platinum-resistant ovarian cancer who have been previously treated with 1 to 3 prior systemic therapies, according to a press release from the drug's developer ImmunoGen.1
The application seeks approval through the accelerated approval pathway, which was created to expedite the development of treatments for severe conditions that provide meaningful advantages. The application is based on results from the phase 3 SORAYA trial (NCT04296890), assessing the agent in the forementioned population, which was presented at The Society of Gynecologic Oncology 2022 Annual Meeting.2 Additionally, ImmunoGen is enrolling patients in a confirmatory phase 3 MIRASOL trial (NCT04209855), comparing mirvetuximab with investigator’s choice of chemotherapy in platinum-resistant advanced high-grade epithelial ovarian, primary peritoneal, or fallopian tube cancers with high FRα expression, which could convert the potential accelerated approval to full approval.
The Prescription Drug User Fee Act date has been set for November 28, 2022.
“FDA’s acceptance of our [biologics license application] under priority review reinforces our belief in the potential for mirvetuximab soravtansine to serve as a new standard of care for patients with FRα-high platinum-resistant ovarian cancer,” Mark Enyedy, ImmunoGen’s president and chief executive officer, said in the press release.
A total of 106 patients were enrolled on the trial, 85 of whom had epithelial ovarian cancer, 8 had fallopian tube cancer, and 12 had primary peritoneal cancer. The majority of patients had stage III disease at diagnosis (n = 63), and most havd unknown or no BRACA mutations (n = 85). More than half of all patients (n = 54) had received a median of 3 prior therapies. All patients had prior exposure to bevacizumab (Avastin; n = 106), and nearly half were treated with PARP inhibitors (n = 51). Patients received mirvetuximab at 6 mg/kg intravenously adjusted for body weight every 3 weeks.
The investigator-assessed objective response rate (ORR), which was the primary end point, was 32.4% (95% CI, 23.6%-42.2%). Of 34 responders, 5 had complete responses and 29 had partial responses. When assessing by patient subgroup, the ORR in those with 1 to 2 lines of prior therapy was 35.3% (95% CI, 22.4%-49.9%) and 30.2% (95% CI, 18.3%-44.3%) for those who received 3 lines of therapy. Those who had prior exposure to PARP inhibitors had an ORR of 38.0% (95% CI, 24.7%-52.8%) vs 27.5% (95% CI, 15.9%-41.7%) for those with no exposure.
The median duration of response (DOR), the study’s secondary end point, was 6.9 months (95% CI, 5.6-8.1). This remained the same for patients who had complete and partial responders. In the subgroup analysis, for those who previously received 1 to 2 lines of prior therapy, the DOR was 5.9 months (95% CI, 4.2-8.1) vs 7.0 months for 3 lines of therapy (95% CI, 3.5–not reached [NR]). For those who had prior PARP inhibitors, the DOR was 5.7 months (95% CI, 3.5-8.1) vs 5.9 months for those who didn’t (95% CI, 3.0-NR).
Treatment-related adverse effects (TRAEs) of any grade occurred in 86% of patients, grade 3 in 27%, and grade 4 in 1%. The most common grade 3 TRAEs included keratopathy (8%), blurred vision (6%), and dry eye (2%). A delay in treatment because of TRAEs was necessary in 32% of patients, with 19% having a dose reduction, and 7% discontinuing treatment. One patient death from respiratory failure was possibly linked to the study treatment; the autopsy showed no evidence of drug reaction, and evidence of lung metastases.
Unique events patients experienced that were specific to mirvetuximab included 7 patients keratopathy, 12 with blurred vision, and 31 who experienced both. The median time to onset was cycle 2 or about 1.5 months. A total of 22% of patients had dose delays or reductions. At data cutoff, more than 80% of patients with grade 2 or 3 events had resolved to grade 0 or 1, 9 of whom were still receiving mirvetuximab or were followed up on for resolution.
Less than 1% of patients discontinued treatment because of ocular events, of which grade 4 keratopathy resolved within 15 days.