FDA Approval Sought for Mirvetuximab Soravtansine in Ovarian Cancer

FDA

A biologics license application (BLA) has been submitted to the FDA for the use of mirvetuximab soravtansine (IMGN853) monotherapy in patients with platinum-resistant ovarian cancer and high folate receptor–alpha (FRα) expression who have received 1 to 3 prior systemic treatments.¹

The application is supported by data from the phase 3 SORAYA trial (NCT04296890), which were presented during the 2022 SGO Annual Meeting on Women’s Cancer. At a data cutoff of November 16, 2021, the antibody-drug conjugate (ADC) was found to produce an investigator-assessed objective response rate (ORR) of 32.4% (95% CI, 23.6%-42.2%) in the overall efficacy population comprised of 105 patients.²

Among the 34 patients who responded to treatment, 5 experienced a complete response (CR) and 29 achieved a partial response (PR). Additionally, 45.7% of patients achieved disease stability and 19.0% experienced progressive disease. The median duration of response (DOR) with the ADC per investigator assessment was 6.9 months (95% CI, 5.6-8.1). The median progression-free survival (PFS) was 4.3 months (95% CI, 3.7-5.1).

“The BLA submission for mirvetuximab soravtansine is a key inflection point on our journey to delivering a safe and effective treatment option to patients with platinum-resistant ovarian cancer and moves us 1 step closer to transforming ImmunoGen into a fully-integrated oncology company,” Mark Enyedy, president and chief executive officer of ImmunoGen, stated in a press release. “Platinum-resistant ovarian cancer is an area with high unmet need, and we look forward to working with FDA to secure mirvetuximab soravtansine’s first approval and bringing this novel therapy to patients as quickly as possible.”

The first-in-class ADC is comprised of a FRα-binding antibody, cleavable linker, and the maytansinoid payload DM4, which allows for targeted killing of cancer cells.

Patients with platinum-resistant ovarian cancer who previously received 1 to 3 regimens and experienced disease recurrence within 6 months following their last dose of platinum therapy were enrolled to the global, single-arm, phase 3 SORAYA trial.

These patients had high-grade serous histology and previously received bevacizumab (Avastin). Additionally, they had tumors that demonstrated FRα-high membrane staining per immunohistochemistry PS2+ scoring. Patients were allowed to have previously received a PARP inhibitor, but they could not have primary platinum-refractory disease.

Patients enrolled to the trial were given the ADC intravenously at 6 mg/kg once every 3 weeks.

Investigator-assessed confirmed ORR served as the primary end point of the trial, as well as ORR by blinded independent central review (BICR) for the planned sensitivity analysis. DOR served as a key secondary end point.

Among the overall population, the median age was 62 years (range, 35-85). The majority of patients (80%) had a primary cancer diagnosis of epithelial cancer, followed by primary peritoneal cancer (11%), and fallopian tube cancer (8%). Fifty-nine percent of patients had stage III disease at the time of their initial diagnosis, 38% had stage IV disease, and 2% had stage I to II disease. Additionally, 20% of patients had tumors that harbored a BRCA mutation.

Fifty-one percent of patients previously received 3 systemic therapies, 39% had received 2, and 9% received 1. All participants received prior bevacizumab and 48% had previously received a PARP inhibitor. Sixty percent of patients had a primary platinum-free interval that ranged from 3 months to 12 months, and 40% had an interval that was longer than 1 year. Moreover, 60% of patients had a platinum-free interval that ranged from 3 months to 6 months, and 37% had an interval that ranged from 0 months to 3 months.

Additional data with mirvetuximab soravtansine that were shared during the meeting indicated that among the 50 patients who previously received a PARP inhibitor, the agent produced an ORR of 38.0% (95% CI, 24.7%-52.8%), with a median DOR of 5.7 months (n = 19; 95% CI, 3.5-8.1). Among the 51 patients who did not previously receive a PARP inhibitor, the ADC elicited an ORR of 27.5% (95% CI, 15.9%-41.7%) with a median DOR of 5.9 months (n = 14; 95% CI, 3.0–not reached [NR]).

The BICR-assessed ORR reported with mirvetuximab soravtansine was 31.6% (95% CI, 22.4%-41.9%) among a total of 95 patients; this included a 5.3% CR rate and a 26.3% PR rate. Additionally, 55.8% of patients achieved stable disease and 8.4% experienced progressive disease. The median DOR per BICR assessment was 11.7 months (95% CI, 5.0-NR). Moreover, the median BICR-assessed PFS was 5.5 months (95% CI, 3.8-6.9) with the ADC.

All-grade toxicities were experienced by 86% of patients, with 27% of patients experiencing effects that were grade 3 in severity and 1% of patients experiencing effects that were grade 4. Most of these toxicities were low-grade, reversible ocular and gastrointestinal events. Serious treatment-related adverse effects (TRAEs) that were grade 3 or higher occurred in 8% of patients.

The grade 3 AEs that were most frequently experienced with mirvetuximab soravtansine comprised keratopathy (8%), blurred vision (6%), dry eye (2%), diarrhea (2%), fatigue (1%), asthenia (1%), decreased appetite (1%), and neutropenia (1%). Grade 4 keratopathy was experienced by 1 patient.

TRAEs resulted in dose delays and reductions for 32% and 19% of patients, respectively. Seven patients discontinued treatment with the ADC because of AEs. One death occurred on the trial and this was determined to potentially be linked with the study treatment; the patient had respiratory failure and an autopsy did not show evidence of a drug reaction although lung metastases were noted.

Forty-seven percent of patients experienced keratopathy and blurred vision, and these effects were flagged to be unique events that are specific to the ADC. Investigators provided patients with supportive care to combat this proactively, and these efforts included the administration of lubricating artificial tears and corticosteroid eye drops. The median time to onset of these toxicities was cycle 2 of treatment, which translated to approximately 1.5 months. These toxicities were noted to be manageable with dose modifications, when required.

Notably, the BLA was submitted under the FDA’s accelerated approval pathway. The regulatory agency has a 60-day review period to determine whether the application is acceptable for filing.

References

1. ImmunoGen submits biologics license application to the US Food and Drug Administration for mirvetuximab soravtansine in ovarian cancer. News release. ImmunoGen, Inc.; March 29, 2022. Accessed March 29, 2022. https://bit.ly/3Nu7Hvo
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. Presented at: 2022 SGO Annual Meeting on Womens’ Cancers; March 18-21, 2022; Phoenix, AZ. Abstract 242.