A pooled analysis of 3 studies showed that there was an extended treatment benefit for patients with FRα positive recurrent ovarian cancer treated with the novel antibody-drug conjugate mirvetuximab soravtansine.
Extended treatment benefit (ETB) was observed in patients with folate receptor alpha (FRα)-positive recurrent ovarian cancer treated with mirvetuximab soravtansine (mirvetuximab) monotherapy, according to the results of a pooled analysis.1
The pooled analysis looked at the findings of the phase 1 IMGN853-0401 trial (NCT01609556), the phase 3 FORWARD I trial (NCT02631876), and the phase 3 SORAYA trial (NCT04296890), that progressively looked at the use of the first in class antibody drug conjugate (ADC) in this patient population. The analysis defined ETB as progression-free survival (PFS) for more than 12 months per investigator assessment, and in the pooled analysis of 466 patients ETB was demonstrated in 40 patients (9%).
Eighty-three percent of patients that demonstrated ETB had stage III disease, 55% had at least 1 line of prior therapy, and 60% had prior exposure to bevacizumab (Avastin). Moreover, ETB occurred mostly in patients with a high FRα expression but did occur in patients with lower FRα expression as well.
Results of the pooled analysis also showed favorable response rates for patients with positive FRα expression, according to a poster presented at the 23rd Congress of the European Society of Gynaecological Oncology (ESGO) in Berlin, Germany. Patients with ETB had an objective response rate (ORR) of 77.5% (n = 31) with 25% (10) of patients having a complete response, but 52.5% (21) achieved a partial response. Moreover, the median duration of this response in patients with ETB was 22.1 months (95% CI, 13.8-60.0) and median PFS was 17 months (95% CI, 16.4-23.1). The remaining 20% (8) of patients with ETB had a best response of stable disease, with only 1 patient deemed not evaluable.
"We believe the study outcomes presented at ESGO support the potential benefit mirvetuximab can have for a subset of patients on a long-term basis and add to the strong, existing foundation of data that supports mirvetuximab’s potential to become the new standard of care for [patients with] FRα-positive ovarian cancer," stated Anna Berkenblit, MD, Senior Vice President and Chief Medical Officer of ImmunoGen, the drug manufacturer, in a press release. "With the PDUFA date for mirvetuximab rapidly approaching, we look forward to the opportunity to bring this novel therapy to patients before the end of this year."
Mirvetuximab is an ADC that has a FRα-binding antibody, cleavable linker, and the maytansinoid payload DM4, which makes it a potent tubulin inhibitor designed to kill the targeted cancer cells in this patient population. The 3 trials in this study have looked at the increasingly effective use of the monotherapy, with the latest results of the single-arm SORAYA trial that had a confirmed ORR of 32.4% (95% CI, 23.6% to 42.2%) among the 106 patients observed.2
“Patients with platinum-resistant ovarian cancer have limited treatment options, and these are associated with low response rates and significant toxicity," 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 separate press release. "With an objective response rate of 32.4%, far exceeding that seen with current therapies, and a median duration of response approaching seven months, mirvetuximab continues to demonstrate impressive efficacy in patients with platinum-resistant disease who have already received bevacizumab.”
In the pooled analysis, investigators found that patients with ETB’s overall adverse event (AE) profile was still consistent with a previously reported integrated safety summary of the 464 patients, and no new safety signals were reported. Within the pooled analysis, AEs were mostly low-grade gastrointestinal and ocular AEs that were resolved with supportive care, and in some cases, dose modifications.
In the SORAYA trial alone, mirvetuximab was well-tolerated with a treatment-related AEs [TRAEs] leading to dose reductions in 19% of patients, dose delays in 32% of patients, and discontinuation in 7% patients. The most common TRAEs were mostly low grade, or grade 3, including blurred vision (41% all grade; 6% grade 3), keratopathy (36% all grade; 8% grade 3 and more), and nausea (29% all grade; 0% grade 3).
"Treatment options for patients with platinum-resistant ovarian cancer are extremely limited and characterized by low activity and considerable toxicity," said Ana Oaknin, head of gynecologic tumors Unit,Vall d'Hebron Institute of Oncology, senior medical oncologist and attending physician, medical oncology department, Vall d'Hebron University Hospital, in a press release from ESGO. "The results from this analysis, coupled with a favorable tolerability and a consistent safety profile, add to the excitement I and many other physicians now have for the potential of mirvetuximab for women with FRα-positive platinum-resistant ovarian cancer."
1. ImmunoGen Presents Retrospective Analysis of Extended Treatment Benefit from Multiple Trials of Mirvetuximab Soravtansine in Ovarian Cancer at ESGO. Immunogen. October 28th, 2022. Accessed: November 1st, 2022. https://yhoo.it/3DQL4yn
2. ImmunoGen Presents Full Results from Positive Pivotal SORAYA Trial of Mirvetuximab Soravtansine in Ovarian Cancer at SGO Annual Meeting. ImmunoGen. March 19th, 2022. Accessed: November 1st, 2022. https://bit.ly/3WoDUsz