FDA Approves Mirvetuximab Soravtansine in FRα-High Platinum-Resistant Ovarian Cancer

The FDA has granted accelerated approval to mirvetuximab soravtansine (Elahere) for patients with folate receptor alpha (FRα)-high platinum-resistant ovarian cancer who have been previously treated with 1 to 3 prior systemic treatments.¹

Approval of the agent is based on findings of the phase 3 SORAYA trial (NCT04296890) which showed the study met its primary end point of achieving meaningful anti-tumor activity with consistent safety and favorable tolerability.

"The approval of Elahere is significant for patients with FRα-positive platinum-resistant ovarian cancer, which is characterized by limited treatment options and poor outcomes," 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. “Elahere’s impressive anti-tumor activity, durability of response, and overall tolerability observed in SORAYA demonstrate the benefit of this new therapeutic option, and I look forward to treating patients with Elahere."

In May 2022, the FDA granted priority review to a biologics license applicationfor mirvetuximab soravtansine in this patient population after top-line data from the phase 3 SORAYA trial that were announced in November 2021. Then, full data were presented at the Society of Gynecologic Oncology (SGO) 2022 Annual Meeting which further supported the BLA for mirvetuximab soravtansine.

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

SORAYA was an open-label, single arm study which evaluated 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.

The study enrolled 106 patients who were treated with mirvetuximab soravtansine monotherapy at 6 mg/kg adjusted by ideal body weight administered on day 1 of every 3-week cycle. Among those enrolled, the median number of prior lines of therapy was 3 as 51% of patients had 3 prior lines of therapy and 48% had 1-2 prior lines of therapy. All patients who were enrolled received prior bevacizumab (Avastin), and 48% of patients received a prior PARP inhibitor.

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 were eligbile for enrollment in the study. Other requirements included 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 function.

The primary end point of the study was objective response rate (ORR) with secondary end points including duration of response (DOR), adverse events, progression-free survival (PFS), overall survival, and CA-125 response.

At the time of the data cutoff of On November 16, 2021, the ORR with mirvetuximab soravtansine was 31.7% (95% CI, 22.9%-41.6%) among patients in the overall efficacy patient population (n = 105). The median DOR was 6.9 months (95% CI: 5.6, 9.7) per investigator assessment.¹

Treatment-related adverse events (TRAEs) led to dose reductions in 19% of patients along with dose delays in 32%, and discontinuations in 7%.² The most common adverse events observed with the agent were laboratory abnormalities, were 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. There AEs were observed in 20% of patients of greater.

"Platinum-resistant ovarian cancer is a notoriously challenging disease to treat. Given there have been no new therapies approved by FDA for this indication since 2014, ELAHERE's accelerated approval is a tremendous advance in the ovarian cancer treatment paradigm,” said Anna Berkenblit, MD, senior vice president and chief medical officer of ImmunoGen, in the press release.¹ “We are thrilled with today’s approval and extend our sincere thanks to the patients, families, caregivers, and investigators who helped make this achievement a reality and have supported the broader mirvetuximab development program. As we work to deliver more good days to patients, we look forward to the continued evaluation of mirvetuximab in earlier lines of treatment, in combination, and across a wider range of levels of FRα expression.”

_References:

_{1. ImmunoGen announces FDA accelerated approval of ELAHERE™ (mirvetuximab soravtansine-gynx) for the treatment of platinum-resistant ovarian cancer. News release. November 14, 2022. Accessed November 14, 2022. https://bit.ly/3O61Flg}

_{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 May 23, 2022. https://clinicaltrials.gov/ct2/show/NCT04296890}