Priority review to a biologics license application has been granted by the FDA for mirvetuximab soravtansine to treat patients with folate receptor alpha-high platinum-resistant ovarian cancer.
The FDA has granted priority review to a biologics license application (BLA) for mirvetuximab soravtansine (IMGN853) to treat patients with folate receptor alpha (FRα)-high platinum-resistant ovarian cancer who have been previously treated with 1 to 3 prior systemic treatments, according to ImmunoGen, Inc.1
Top-line data from the phase 3 SORAYA trial that were announced in November 2021 and full data that were presented at the Society of Gynecologic Oncology (SGO) 2022 Annual Meeting supported the BLA for mirvetuximab soravtansine, as the agent met the study’s primary end point of achieving meaningful anti-tumor activity with consistent safety and favorable tolerability.
“[The] FDA’s acceptance of our BLA 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,” said Mark Enyedy, chief executive officer and president of ImmunoGen, in a press release. “We are pleased to be 1 step closer to realizing the promise of our technology and are working closely with [the] FDA to support the evaluation of our application. We are moving quickly to build out the commercial and medical infrastructure required for a successful launch and look forward to the prospect of delivering mirvetuximab soravtansine to patients later this year.”
Mirvetuximab soravtansine is a first-in-class antibody-drug conjugate which consists of a folate receptor alpha-binding antibody, cleavable linker, and the maytansinoid payload DM4, a potent tubulin-targeting agent, in order to kill the targeted cancer cells.2
The open-label, single arm study aimed to evaluate the safety and efficacy of mirvetuximab soravtansine in patients with platinum-resistant high-grade serous epithelial ovarian cancer, primary peritoneal, or fallopian tube cancer, whose tumors express a high-level of FRα.
A total of 106 patients were enrolled in the study and treated with mirvetuximab soravtansine monotherapy at 6 mg/kg adjusted by ideal body weight administered on day 1 of every 3-week cycle. Patients were assessed for the primary end point of objective response rate (ORR), and secondary end points included duration of response (DOR), adverse events, progression-free survival (PFS), overall survival, and CA-125 response.
Of the 106 patients enrolled, the median number of prior lines of therapy was 3 with 51% having 3 prior lines of therapy and 48% having 1 to 2 prior lines of therapy. All patients received prior bevacizumab (Avastin), and 48% of patients received a prior PARP inhibitor.
Enrollment was open to female patients aged 18 years and older with a confirmed diagnosis of high-grade serous epithelial ovarian cancer, primary peritoneal cancer, or fallopian tube cancer. Other requirements for eligibility in the study included patients having progressed radiographically on or after their most recent line of anticancer therapy, an ECOG performance status of 0-1, at least 1 lesion that meets the definition of measurable disease by RECIST v1.1, and adequate hematologic, liver and kidney functions.
On November 16, 2021, the time of the data cut-off, mirvetuximab soravtansine demonstrated an ORR of 32.4% (95% CI, 23.6%-42.2%) within the overall efficacy patient population (n = 105). Five patients who responded to the antibody drug conjugate achieved a complete response (CR), and 29 patients experienced a partial response (PR). A total of 45.7% of patients were shown to have stable disease (SD), and 19.0% experienced disease progression. The median DOR was 6.9 months (95% CI, 5.6-8.1), and the median PFS was 4.3 months (95% CI, 3.7-5.1).
In the group of patients who had previously received 1 to 2 lines of treatment, mirvetuximab soravtansine achieved an ORR of 35.3% (95% CI, 22.4%-49.9%), with a 5.9-month median DOR (95% CI, 4.2-8.1). Among patients who received 3 prior lines of treatment, mirvetuximab soravtansine induced an ORR of 30.2% (95% CI, 18.3%-44.3%), with a median DOR of 7.0 months (n = 16; 95% CI, 3.5-not reached [NR]).
For patients who previously received a PARP inhibitor, the ORR with mirvetuximab soravtansine was 38.0% (95% CI, 24.7%-52.8%), and the median DOR was 5.7 months (n = 19; 95% CI, 3.5-8.1) compared with those not previously exposed to a PARP inhibitor who had an ORR of 27.5% (95% CI, 15.9%-41.7%) with the agent, and a median DOR of 5.9 months (n = 14; 95% CI, 3.0-NR).
ORR assessed by blind independent review committee (BICR) was 31.6% (95% CI, 22.4%-41.9%) in a total of 95 patients, and included a CR rate of 5.3% and a PR rate of 26.3%. A total of 55.8% of patients achieved SD, and 8.4% experienced disease progression. Additionally, the BICR-assessed median DOR was 11.7 months (95% CI, 5.0-NR), and the BICR-assessed median PFS was 5.5 months (95% CI, 3.8-6.9).
In regard to safety, treatment-related adverse events (TRAEs) resulted in dose reductions in 19% of patients, dose delays in 32%, and discontinuations in 7%. The TRAEs that were most commonly observed included low-grade and generally reversible, including blurred vision, keratopathy, and nausea. Overall, mirvetuximab had a well-tolerated safety profile that was consistent with previous findings.
ImmunoGen is currently also enrolling patients into the confirmatory MIRASOL trial. The potential accelerated approval is expected to convert to full approval, and top-line data from this study is expected to be released in early 2023.