Phase 3 Trial Further Examines Maintenance Mirvetuximab Soravtansine in Ovarian Cancer

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As part of the phase 3 GLORIOSA study (NCT05445778), a clinical trial is evaluating the safety and efficacy of the antibody drug conjugate (ADC) mirvetuximab soravtansine (Elahere) as maintenance therapy for patients with folate receptor-alpha (FRα)-positive recurrent platinum-sensitive ovarian cancer.¹

In the multicenter, open-label GLORIOSA trial, investigators are evaluating mirvetuximab soravtansine in combination with bevacizumab (Avastin) compared with bevacizumab alone as maintenance therapy for patients with platinum-sensitive ovarian, primary peritoneal, or fallopian tube cancers.

Mirvetuximab soravtansine is a first-in-class ADC for the treatment of recurrent platinum-sensitive ovarian cancer that overexpresses FRα, a protein found in several cancers. The agent binds a monoclonal antibody, which targets FRα on the surface of tumor cells, with a cytotoxic drug molecule called DM4. When it is inside of the cancer cell, DM4 disrupts the formation of microtubules and kills the cancer cells. At the same time, it leaves normal cells intact.

Treatment with mirvetuximab soravtansine elicited improved responses when used for the treatment of patients with FRa-high platinum-resistant ovarian cancer. These findings were observed in the phase 3 SORAYA trial (NCT04296890) and showed that for a median follow-up of 13.4 months, objective anti-cancer responses were seen in 32.4% of patients. Five of these patients had a complete response and 29 had a partial response (95% CI, 23.6-42.2). Additionally, the median duration of response (DOR) in the study was 6.9 months (95% CI, 5.6-9.7) and mirvetuximab was well-tolerated with the most common adverse events (AEs) being blurred vision, keratopathy, and nausea.²

As a result of these positive findings, the FDA granted accelerated approval to mirvetuximab soravtansine in November 2022.

Additionally, previous studies of bevacizumab showed that the agent alone prolonged progression-free survival (PFS) in the first- and second-line treatment for patients with platinum-sensitive ovarian cancer who had not received previous treatment with bevacizumab. According to the press release and Pothuri, the role of frontline PARP inhibitor (PARPi) maintenance therapy in ovarian cancer can be considered a new standard of care for patients with ovarian, fallopian tube, and peritoneal cancer who have had a response to platinum-based therapy.

“As more patients are getting PARP [inhibitor] in the frontline setting, newer maintenance options are needed in the recurrent setting,” said Bhavana Pothuri, MD, professor in the Department of Obstetrics and Gynecology and Department of Medicine at NYU Grossman School of Medicine, and director of Gynecologic Oncology Clinical Trials at NYU Langone Health’s Perlmutter Cancer Center, in a press release¹. “Adding mirvetuximab soravtansine to bevacizumab makes a lot of rational sense.”

In the phase 3 study assessing bevacizumab alone vs in combination with mirvetuximab soravtansine, investigators are enrolling approximately 418 patients with recurrent platinum-sensitive, high-grade epithelial ovarian, primary peritoneal, or fallopian tube cancers, with high FRα expression, and confirmation of FRα positivity by the Ventana FOLR1 Assay.³

Patients aged 18 years and older with an ECOG performance status of 0-1, who have had BRCA testing on the tumor or prior germline testing, and who have relapsed after 1 line of platinum-based chemotherapy and have platinum-sensitive disease are eligible for enrollment in the study. Inclusion in the trial is open to patients with adequate hematologic, liver, and kidney functions, those who have completed any major surgery at least 4 weeks before the first dose of maintenance treatment and who have recovered from the adverse events of prior surgery before the first dose of maintenance treatment, and those who have stabilized or recovered to grade 1 or baseline from all prior therapy-related toxicities.

The primary end point of the study is PFS with secondary end points including overall survival, safety, tolerability, second disease progression, objective response rate, duration of response, disease-free survival, pharmacokinetics, and patient-reported outcomes.

The trial is ongoing at NYU Langone Health’s Perlmutter Cancer Center and has an estimated study completion date of April 2029.

“The [FDA] has narrowed the treatment indication with PARPi in the maintenance setting of ovarian cancer, limiting the use of niraparib and rucaparib to patients who have a BRCA gene mutation,” added Pothuri, in the press release¹. “Combining mirvetuximab soravtansine and bevacizumab represents a new treatment option for patients who are beyond just having a BRCA mutation, which represents 75% of ovarian cancers.”

REFERENCES:

1. Perlmutter cancer center clinical trial tests antibody–drug conjugate targeting the folate receptor in platinum-sensitive ovarian cancer. News release. NYU Langone Health. March 31, 2023. Accessed April 11, 2023. https://bit.ly/3MD0R8L

2. Matulonis UA, Lorusso D, Oaknin A, et al. Efficacy and safety of mirvetuximab soravtansine in patients with platinum-resistant ovarian cancer with high folate receptor alpha expression: results from the SORAYA study. Published online January 30, 2023. J Clin Oncol. 2023;JCO2201900. doi:10.1200/JCO.22.01900

3. Mirvetuximab soravtansine with bevacizumab versus bevacizumab as maintenance in platinum-sensitive ovarian, fallopian tube, or peritoneal cancer (GLORIOSA). ClinicalTrials.gov. Updated December 20, 2022. Accessed April 11, 2023.