SORAYA Trial Meets Primary End Point of ORR in Ovarian Cancer

Mirvetuximab soravtansine (IMGN853) demonstrated meaningful anti-tumor activity with consistent safety and favorable tolerability in patients with folate receptor alpha (FRα)–high platinum-resistant ovarian cancer who have been previously treated with bevacizumab (Avastin), meeting the primary end point of the SORAYA trial (NCT04296890), according to a press release from ImmunoGen, Inc.¹

Results were presented by 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, during the the Society of Gynecologic Oncology (SGO) 2022 Annual Meeting on Women’s Cancer.

"Patients with platinum-resistant ovarian cancer have limited treatment options, and these are associated with low response rates and significant toxicity," Matulonis said in the 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. The anti-tumor activity and consistent safety and tolerability data from the SORAYA trial further underscore the potential of mirvetuximab, if approved, to become a practice-changing, biomarker-driven standard of care for these patients."

The phase 3, single-arm study enrolled 106 patients and examined mirvetuximab in patients with platinum-resistant ovarian cancer treated with 1 to 3 prior regimens.² These patients also experienced recurrence within 6 months after the last platinum dose they had received. All patients received mirvetuximab soravtansine at 6 mg/kg adjusted ideal body weight administered on day 1 of every 3-week cycle.

To be eligible for enrollment, patients were required to be female aged 18 and older, have high-grade serous histology and have received prior bevacizumab. Patients also needed to have tumors that demonstrated FRα-high membrane staining with immunohistochemistry PS2+ scoring, and patients were allowed to have received a prior PARP inhibitor. However, those with primary platinum-refractory disease were excluded.

The primary end point of the study was confirmed objective response rate (ORR) as assessed by investigators with a key secondary end point of duration of response (DOR). ORR was also assessed by a blinded independent central review (BICR).

Of the 106 participants with a median of 3 prior lines of therapy, 51% had 3 prior lines of therapy and 48% had 1 to 2 prior lines of therapy. All patients received prior bevacizumab, and 48% of patients received a prior PARP inhibitor.

Findings revealed that at a data cutoff of November 16, 2021, the antibody-drug conjugate (ADC) had an ORR of 32.4% (95% CI, 23.6%-42.2%) in the overall efficacy patient population (n = 105). Of the 34 responders, 5 patients achieved a complete response (CR), and 29 patients experienced a partial response (PR). Additionally, 45.7% of patients achieved stable disease (SD), and 19.0% experienced disease progression. The median DOR was 6.9 months (95% CI, 5.6-8.1) with the agent, and the median progression-free survival (PFS) with mirvetuximab soravtansine was 4.3 months (95% CI, 3.7-5.1).

Among the group of patients who had previously received 1 to 2 lines of treatment (n = 51), the ADC induced an ORR of 35.3% (95% CI, 22.4%-49.9%), and the median DOR reported was 5.9 months (n = 18; 95% CI, 4.2-8.1). For participants who received 3 prior lines of treatment (n = 53), mirvetuximab soravtansine elicited an ORR of 30.2% (95% CI, 18.3%-44.3%), with a median DOR of 7.0 months (n = 16; 95% CI, 3.5-not reached [NR]).

Of those who previously received a PARP inhibitor (n = 50), the ORR achieved with the ADC was 38.0% (95% CI, 24.7%-52.8%), and the median DOR was 5.7 months (n = 19; 95% CI, 3.5-8.1). Those who were not previously exposed to a PARP inhibitor (n = 51) demonstrated that mirvetuximab soravtansine produced 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-NR).

Additionally, data showed that the BICR-assessed ORR achieved with the ADC was 31.6% (95% CI, 22.4%-41.9%) among 95 patients, which included a CR rate of 5.3% as well as a PR rate of 26.3%. A total of 55.8% of patients achieved SD, and 8.4% experienced disease progression. The BICR-assessed median DOR was 11.7 months (95% CI, 5.0-NR), and the BICR-assessed median PFS was 5.5 months (95% CI, 3.8-6.9).

In regard to safety, mirvetuximab was well-tolerated and consistent with the known safety profile. Treatment-related adverse events (TRAEs) led to dose reductions in 19% of patients, dose delays in 32% of patients, and discontinuations in 7% of patients. Overall, the most common TRAEs were reported as being low-grade and generally reversible, including blurred vision, keratopathy, and nausea

ImmunoGen Inc. plans to submit a Biologics License Application to the FDA later this month based on the concluded data.

REFERENCES:

1. ImmunoGen Presents Full Results from Positive Pivotal SORAYA Trial of Mirvetuximab Soravtansine in Ovarian Cancer at SGO Annual Meeting. News Release. ImmunoGen, Inc. March 19, 2022. Accessed March 22, 2022.

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 March 22, 2022. https://clinicaltrials.gov/ct2/show/NCT04296890?term=NCT04296890&draw=2&rank=1