The novel antibody-drug conjugate mirvetuximab soravtansine could become the new standard of care for patients with folate receptor alpha–positive, platinum-resistant ovarian cancer, according to data presented at the Society of Gynecologic Oncology (SGO) 2022 Annual Meeting on Women’s Cancer.1
Results of the phase III SORAYA study showed an overall response rate of 32.4%, including five complete responses, for patients who received mirvetuximab soravtansine. The median duration of response with mirvetuximab soravtansine was 6.9 months, and consistent response rates were seen regardless of the number of prior therapies or the use of a prior PARP (poly [ADP-ribose] polymerase) inhibitor.
Ursula A. Matulonis, MD
“The response rate is nearly triple the benchmark set in prior studies of less heavily pretreated, platinum-resistant ovarian cancer populations,” said lead study author Ursula A. Matulonis, MD, Chief of the Division of Gynecologic Oncology at the Dana-Farber Cancer Institute and Professor of Medicine at Harvard Medical School. “These results position mirvetuximab soravtansine to become a practice-changing, biomarker-driven standard-of-care treatment option for patients with folate receptor alpha–positive, platinum-resistant ovarian cancer.”
As Dr. Matulonis explained, treatment options for platinum-resistant ovarian cancer are limited, consisting primarily of single-agent chemotherapy, as many patients will have received prior bevacizumab. With an overall response rate of between 4% and 13%, however, single-agent chemotherapy has limited activity and considerable toxicity, and no biomarker-directed therapy is indicated specifically for patients with platinum-resistant disease.
Mirvetuximab soravtansine is a first-in-class antibody-drug conjugate comprising a folate receptor alpha–binding antibody, a cleavable linker, and maytansinoid DM4 (a tubulin-targeting agent). The folate receptor protein is far more abundant in some tumor cells than in normal cells, making it an attractive target for cancer drugs, said Dr. Matulonis. She also noted that folate receptor alpha is highly expressed in up to 40% of all high-grade serous cancers.
Mirvetuximab soravtansine is not yet approved for use outside a clinical trial.
SORAYA is a global, single-arm, phase III study evaluating mirvetuximab soravtansine in adults with folate receptor alpha–high, platinum-resistant, high-grade, serous epithelial ovarian, primary peritoneal, or fallopian tube cancer. The primary endpoint is confirmed investigator-assessed overall response rate, and the key secondary endpoint is duration of response.
Patients had received one to three prior therapies, prior bevacizumab was required, and prior PARP inhibitors were allowed. Patients with primary platinum-refractory ovarian cancer were ineligible, but those with secondary platinum-refractory ovarian cancer could be enrolled. Using immunohistochemistry-based scoring, the investigators evaluated available archival tumor tissue for folate receptor alpha expression. Patients were eligible for the study if at least 75% of cells had 2+ staining intensity or greater. Mirvetuximab soravtansine was given intravenously at 6 mg/kg using adjusted ideal body weight once every 3 weeks until disease progression or intolerable side effects.
Of the 106 patients enrolled, 38% had stage IV disease at initial diagnosis, 51% had received three prior therapies, and 48% received a prior PARP inhibitor.
One-Third of Patients Achieved Remission
The confirmed investigator-assessed objective response rate was 32.4%, including 5 complete responses and 29 partial responses. According to Dr. Matulonis, these outcomes far exceed the single-digit response rates observed with current treatments for patients with ovarian cancer that is unresponsive to platinum-based chemotherapy.
In prespecified subgroup analyses, the objective response rate was also consistent regardless of the number of prior therapies or prior exposure to PARP inhibition. The overall response rate was 35% in patients who had one to two prior lines and 30% in patients who had three prior lines. For patients who had received a prior PARP inhibitor, the overall response rate was 38% vs 27.5% for those who had not.
The median duration of response is 6.9 months, with seven responses ongoing at the time of data cutoff (March 3, 2022). “These responses are rapid and durable,” said Dr. Matulonis, who reported a 5.5-month median progression-free survival as assessed by blinded independent central review.
Safety and Tolerability Profile
The safety and tolerability profile of mirvetuximab soravtansine was also consistent with that observed in previous studies. The most common treatment-related adverse events were low-grade, reversible ocular and gastrointestinal (GI) events, which were manageable with supportive care. There was a low incidence of peripheral neuropathy, no appreciable myelosuppression, and a limited number of hematologic events. Serious grade 3 and higher events were reported in 8% of patients, and seven patients (7%) discontinued treatment due to treatment-related adverse events.
Although ocular events are common with antibody-drug conjugates, not all antibody-drug conjugates are the same, reminded Dr. Matulonis. “The ocular events observed with mirvetuximab soravtansine were reversible and primarily included low-grade blurred vision and keratopathy, which were managed with protocol-defined dose modifications,” she reported. “Approximately 60% of patients with symptoms had resolution of these symptoms prior to their next cycle of treatment, and less than 1% of patients discontinued therapy due to an ocular event.”
“These data have the potential to be transformative for [patients with] ovarian cancer and their physicians,” Dr. Matulonis concluded.
DISCLOSURE: Dr. Matulonis reported financial relationships with Novartis, AstraZeneca, Merck, GSK, Trillium, Blueprint Medicines, Agenus, ImmunoGen, NextCure, Ovarian Cancer Research Alliance, Rivkin Foundation, Clearity, Symphogen, Alkermes, and Advaxis.
1. 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. 2022 SGO Annual Meeting on Women’s Cancer. Abstract 242. Presented March 19, 2022.
Deborah K. Armstrong, MD
Discussant of the SORAYA trial, Deborah K. Armstrong, MD, of Johns Hopkins Kimmel Cancer Center Baltimore, underscored the strong rationale for targeting folate receptor alpha in ovarian cancer.
“There is limited expression [of folate receptor alpha] in normal...