Top-line results from the phase 3 SORAYA study show promise for mirvetuximab in patients with FRα-high platinum-resistant ovarian cancer.
Single-agent mirvetuximab soravtansine (mirvetuximab; IMGN853) has demonstrated clinically meaningful benefit in patients with late receptor alpha (FRα)-high platinum-resistant ovarian cancer who have been previously treated with bevacizumab (Avastin), according to top-line results from the phase 3 SORAYA clinical trial.1
"Despite advances in the platinum-sensitive setting, most patients with ovarian cancer eventually develop platinum-resistant disease, for which there are limited treatment options, especially for those patients who have previously received bevacizumab," said Robert Coleman, MD, chief scientific officer of US Oncology Research and SORAYA co-principal investigator, in a press release. "Data from SORAYA have the potential to redefine the standard of care for patients with FRα-high platinum-resistant ovarian cancer, as this trial has demonstrated that mirvetuximab delivers clinically meaningful benefit in this setting, with significant and durable responses and a favorable tolerability profile.”
In the single-arm study, patients received mirvetuximab 6 mg/kg adjusted ideal body weight administered on day 1 of every 3-week cycle. The primary end point investigated was objective response rate (ORR), and the protocol is designed to rule out a 12% ORR, based on expected outcomes with available single-agent chemotherapy from the AURELIA study (NCT00976911) in patients with platinum-resistant ovarian cancer who were previously treated with 1 to 2 therapies. The secondary end points included duration of response (DOR), adverse events (AEs), progression-free survival, overall survival, and CA-125 response.1,2
Overall, 106 patients were enrolled, and the cohort had 3 prior lines of therapy, (range,1-4). Fifty-one percent of patients have received 3 prior lines of therapy, and 48% had 1 or 2 prior lines. All patients enrolled were previously treated with bevacizumab and 48% had prior PARP inhibitor therapy.1
At a median follow-up of 8.1 months, mirvetuximab achieved an ORR of 32.4% (95% CI, 23.6%-42.2%), which included complete responses in 5 patients. ORR evaluated per blinded independent review was 31.6% (95% CI, 22.4%-41.9%). Responses were irrespective of prior PARP inhibitor treatment or the number of prior lines of therapy.
The median DOR at the data cutoff of November 16, 2021, was 5.9 months (95% CI: 5.6-7.7), and more than 50% of patients were continuing to respond with long-term follow-up.
In terms of safety, treatment with mirvetuximab was well tolerated with events associated with the known safety profile of the drug. Treatment-related AEs (TRAEs) led to dose reductions in 19% of patients, dose delays were observed in 32% of patients, and treatment discontinuations occurred in 7% of patients. The most common any-grade TRAEs were blurred vision (41%) keratopathy (355), and nausea (29%), and these same TRAEs were grade 3 in severity for 6%, 9%, and 0%, respectively.
"These data have the potential to be transformative for ovarian cancer patients and their physicians," said Ursula Matulonis, MD, chief of the Division of Gynecologic Oncology at the Dana-Farber Cancer Institute, professor of Medicine at the Harvard Medical School, and SORAYA co-principal investigator, in a press release "In the platinum-resistant setting and particularly in later-line treated patients, response rates with available therapy are in the single digits with significant toxicities. With an ORR above 30%, a duration of response of around six months, and a treatment-related discontinuation rate below 10%, mirvetuximab shows impressive activity and tolerability for patients with platinum-resistant ovarian cancer. If approved, mirvetuximab will become a critical therapeutic option for patients with FRα-high ovarian cancer."
Regarding the results, Anna Berkenblit, MD, senior vice president, and chief medical officer of ImmunoGen stated in the press release: "We are extremely pleased with the top-line data from SORAYA, which support our strategy to position mirvetuximab as the standard of care for patients with FRα-high ovarian cancer. This is particularly encouraging given the majority of patients in SORAYA were fourth-line, and the safety profile and anti-tumor activity replicate those previously generated in the program. We are deeply grateful to all of the patients and physicians who participated in this study, and we look forward to presenting the full SORAYA data at a medical meeting next year."
1. ImmunoGen announces positive top-line results from pivotal SORAYA trial of mirvetuximab soravtansine in ovarian cancer. News release. ImmunoGen. November 30, 2021. Accessed November 30, 2021.https://bit.ly/3d2H8MC
2. A study of mirvetuximab soravtansine in platinum-resistant, advanced high-grade epithelial ovarian, primary peritoneal, or fallopian tube cancers with high folate receptor-alpha expression (SORAYA). Clinicaltrials.gov. Accessed November 30, 2021.