Biologics License Application Submitted to FDA for Mirvetuximab Soravtansine in FRα-High Ovarian Cancer

A biologics license application for mirvetuximab soravtansine was submitted to the FDA for patients with folate receptor α–high platinum-resistant ovarian cancer who have previously been treated with 1 to 3 lines of systemic treatments, according to a press release from ImmunoGen Inc.¹

The application is based off results from the phase 3 SORAYA trial (NCT04296890)which was previously presented at The Society of Gynecologic Oncology 2022 Annual Meeting.² Investigators observed an objective response rate (ORR) of 32.4% (95% CI, 23.6%-42.2%) in the overall population. ImmunoGen also filed for priority review, and if the application is accepted, it will be reviewed within 6 months.

"The [biologics license application] 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 one step closer to transforming ImmunoGen into a fully-integrated oncology company," Mark Enyedy, president and chief executive officer of ImmunoGen, said in a press release.

The single-arm trial assessed mirvetuximab in patients with platinum-resistant high-grade serous epithelial ovarian cancer, primary peritoneal cancer, or fallopian tube cancer. Patients received mirvetuximab at 6 mg/kg intravenously with adjusted body weight once every 3 weeks. The primary end point was confirmed ORR and the secondary end point was duration of response (DOR).

In total, 106 patients with a median age of 62 years were enrolled. The majority of patients had epithelial ovarian cancer (80%), followed by primary peritoneal cancer (11%), and fallopian tube cancer (8%). Additionally, most patients had stage IV disease at initial diagnosis (38%). Most patients had no BRCA mutation or an unknown mutational status (80%). Fifty-one percent of patients had 3 lines of prior therapy.

Prior exposure to therapy included bevacizumab (Avastin; 100%) and PARP inhibitors (48%). A primary platinum-free interval of 3 to 12 months was reported in 60% of patients and 40% had an interval of 12 months or more.

Among responders in the overall efficacy population, 5 had complete responses and 29 had partial responses.

In the subgroup analysis, patients who had 1 to 2 lines of prior therapy (n = 51) had an ORR of 35.3% (95% CI, 22.4%-49.9%) and those with 3 prior lines of therapy (n = 53) had an ORR of 30.2% (95% CI, 18.3%-44.3%). Those with prior exposure to PARP inhibitors (n = 50) had an ORR of 38.0% (95% CI, 24.7%-52.8%) and those who had not been treated with PARP (n = 51) had an ORR of 27.5% (95% CI, 15.9%-41.7%).

Additionally, the investigator-assessed median DOR was 6.9 months (95% CI, 5.6-8.1). This remained unchanged for patients who had complete and partial responses, as well.

The subgroup analysis for median DOR found that those with 1 to 2 lines of prior therapy (n = 18) had a DOR of 5.9 months (95% CI, 4.2-8.1) and those with 3 lines of prior therapy (n = 16) had a DOR of 7.0 months (95% CI, 3.5–not reached [NR]). Those with prior exposure to PARP inhibitors (n = 19) had a DOR of 5.7 months (95% CI, 3.5-8.1) and those who had not (n = 14) had a DOR of 5.9 months (95% CI, 3.0-NR).

Grade 3 treatment-related adverse effects (TRAEs) occurred in 27% of patients, and grade 4 TRAEs were reported in 1%. The most common grade 3 TRAEs were keratopathy (8%), blurred vision (6%), and dry eye (2%). TRAEs delayed treated in 32% of patients, and 19% had a dose reduction, with 7% discontinuing treatment entirely. Additionally, 1 patient died potentially due to treatment.

Unique events related to treatment included blurred vision and keratopathy, with 31 patients experiencing both. Patients typically experienced these TRAEs at a median of 2.0 months from onset of treatment, and 22% of patients had related dose delays or reductions. At the time of data cutoff, over 80% of patients had grade 2 or 3 TRAEs that resolved to grade 0 or 1, and 9 patients were still be monitored in follow-up for resolution.

Less than 1% of patients had discontinued treatment because of ocular events, which resolved within 15 days.

References

1. ImmunoGen submits biologics license application to the US Food and Drug Administration for mirvestuximab sorvtansine in ovarian cancer. News Release. ImmunoGen. March 29, 2022. Accessed March 29, 2022. https://yhoo.it/3IOt4nD
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.