Phase 3 SOROYA trial revealed promising response rates with mirvetuximab soravtansine in patients with platinum-resistant ovarian cancer and high folate receptor–alpha expression.
Clinically meaningful antitumor activity and an acceptable safety profile were seen with the use of mirvetuximab soravtansine in patients with platinum-resistant ovarian cancer harboring high folate receptor–alpha (FRα) expression, according to the results of the phase 3 SORAYA trial (NCT04296890) presented during the The Society of Gynecologic Oncology (SGO) 2022 Annual Meeting on Women’s Cancer.
At a data cutoff of November 16, 2021, the antibody-drug conjugate (ADC) elicited an investigator-assessed objective response rate (ORR) of 32.4% (95% CI, 23.6%-42.2%) in the overall efficacy patient population (n = 105). Among the 34 responders, 5 patients achieved a complete response (CR), and 29 patients experienced a partial response (PR); 45.7% of patients achieved stable disease (SD), and 19.0% experienced disease progression.
The median investigator-assessed duration of response (DOR) was 6.9 months (95% CI, 5.6-8.1) with the agent. Moreover, the median progression-free survival (PFS) with mirvetuximab soravtansine was 4.3 months (95% CI, 3.7-5.1).
“These results position mirvetuximab soravtansine to become a practice-changing, biomarker-driven, standard-of-care treatment option for patients with FRα-positive, platinum-resistant ovarian cancer,” lead study author Ursula A. Matulonis, MD, who is also the chief of the Division of Gynecologic Oncology, Brock-Wilson Family Chair, and physician at Dana-Farber Cancer Institute, as well as the professor of medicine at Harvard Medical School, said in a presentation on the data.
Patients with platinum-resistant ovarian cancer have limited therapeutic options available to them. Treatment is largely comprised of single-agent chemotherapy, which is known to have limited efficacy, with ORRs ranging from just 4% and 13%, and substantial toxicity. No biomarker-driven approaches have been indicated for this population.
Mirvetuximab soravtansine is comprised of an FRα-binding antibody, a cleavable linker, and maytansinoid DM4. Findings from a pooled analysis of prior studies that examined the ADC showed that the agent elicited an ORR of 31.4%, a median DOR of 7.8 months, and a median PFS of 4.4 months in 70 patients with FRα-high, platinum-resistant ovarian cancer who previously received 1 to 3 therapies, which included bevacizumab (Avastin).
The global, single-arm, phase 3 SORAYA trial enrolled patients with platinum-resistant ovarian cancer who were treated with 1 to 3 prior regimens and experienced recurrence within 6 months after the last platinum dose they had received.
To be eligible for enrollment, patients needed to have high-grade serous histology and have received prior bevacizumab. Patients needed to have tumors that demonstrated FRα-high membrane staining with immunohistochemistry PS2+ scoring. Notably, patients were allowed to have received a prior PARP inhibitor, but those with primary platinum-refractory disease were excluded.
Study participants were administered intravenous mirvetuximab soravtansine at a dose of 6 mg/kg given once every 3 weeks.
The primary end point of the trial was confirmed ORR per investigator assessment, and ORR by blinded independent central review (BICR) for the sensitivity analysis. A key secondary end point of the trial was DOR.
The median age of study participants was 62 years (range, 35-85). Eighty percent of patients had a primary cancer diagnosis of epithelial ovarian cancer, 11% had primary peritoneal cancer, and 8% had fallopian tube cancer. Most patients (59%) had stage III disease at initial diagnosis, 38% had stage IV disease, and 2% had stage I to II disease. Twenty percent of patients had tumors that harbored a BRCA mutation.
Moreover, 51% of patients received 3 prior systemic therapies, 39% received 2 prior lines, and 9% received 1 prior line of treatment. All patients received prior bevacizumab, and 48% of patients previously received a PARP inhibitor. Sixty percent of patients had a primary platinum-free interval ranging from 3 months to 12 months, and 40% had an interval of longer than 12 months. Sixty percent of patients had a platinum-free interval ranging from 3 months to 6 months, and 37% of patients had a platinum-free interval ranging from 0 months to 3 months.
Among the subset of patients who 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 was 5.9 months (n = 18; 95% CI, 4.2-8.1) In those 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]).
Among 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). In those who were not previously exposed to a PARP inhibitor (n = 51), 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).
Additional 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% and a PR rate of 26.3%. Moreover, 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).
Regarding safety, all-grade toxicities were experienced by 86% of patients; these effects were grade 3 in 27% of patients and grade 4 in 1% of patients. The majority of adverse effects (AEs) were low-grade, reversible ocular and gastrointestinal events. Serious grade 3 or higher treatment-related AEs (TRAEs) were experienced by 8% of patients.
Specifically, the most common grade 3 effects experienced by those who received mirvetuximab soravtansine included keratopathy (8%), blurred vision (6%), dry eye (2%), diarrhea (2%), fatigue (1%), asthenia (1%), decreased appetite (1%), and neutropenia (1%). One patient experienced grade 4 keratopathy.
Thirty-two percent of patients experienced TRAEs that resulted in dose delays, and 19% had TRAEs that required dose reductions. A total of 7 patients discontinued treatment with the ADC because of toxicity. One death occurred on the trial and was determined to potentially be associated with the study treatment; this patient experienced respiratory failure, and an autopsy did not reveal any evidence of drug reaction. Lung metastases were observed.
Keratopathy and blurred vision were flagged as unique events that were specific to mirvetuximab soravtansine, with 47% of patients experiencing these events. Patients were provided with proactive supportive care, which included lubricating artificial tears and corticosteroid eye drops. The median time to onset was cycle 2, which equated to approximately 1.5 months.
These effects were noted to be manageable with dose modifications, if needed. Twenty-two percent of 106 patients had a dose delay and/or reduction. At the time of data cutoff, less than 80% of patients had their grade 2 or 3 effects resolve to grade 0 or 1. Nine patients were still receiving the ADC or were being followed up for resolution.
Notably, less than 1% of patients had to discontinue treatment because of ocular toxicities. One patient discontinued treatment because they experienced grade 4 keratopathy; however, this effect resolved within 15 days.
“The safety and tolerability profile of mirvetuximab soravtansine in SORAYA is consistent with what observed in previous studies,” Matulonis concluded.
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.