The antibody-drug conjugate mirvetuximab soravtansine has shown promising response rates and a favorable toxicity profile in patients with folate receptor alpha (FRα)-high, platinum-resistant ovarian cancer who have received previous treatment with bevacizumab (Avastin), according to topline results from the phase 3 SORAYA trial (NCT04296890) released by ImmunoGen Inc.
Results showed that the trial met its primary end point, with a confirmed objective response rate (ORR) of 32.4% (95% CI, 23.6%-42.2%) per investigator assessment, and 31.6% (95% CI, 22.4%-41.9%) per blinded independent central review (BICR). Both the investigator- and BICR-assessed ORR included 5 complete responses (CRs). Furthermore, the median duration of response (DOR) was 5.9 months (95% CI, 5.6-7.7).
“Despite advances in the platinum-sensitive setting, most patients with ovarian cancer eventually develop platinum-resistant disease, for which there are limited treatment options, especially for those patients who have previously received bevacizumab,” Robert Coleman, MD, co-principal investigator, and chief scientific officer of US Oncology Research, said in a press release. “Data from SORAYA have the potential to redefine the standard of care for patients with FRα-high platinum-resistant ovarian cancer, as this trial has demonstrated that mirvetuximab delivers clinically meaningful benefit in this setting, with significant and durable responses and a favorable tolerability profile.”The SORAYA trial is a single-arm study examining mirvetuximab soravtansine in patients with platinum-resistant ovarian cancer whose tumors express high levels of FRα. Patients enrolled on the study had received up to 3 prior treatment regimens, at least 1 of which included bevacizumab. Additionally, eligible patients had to be 18 years of age or older, have an ECOG performance status of 0 or 1, and have at least 1 lesion that met the definition of measurable disease by RECIST version 1.1 criteria.
Patients with endometrioid, clear cell, mucinous, or sarcomatous histology, or low-grade/borderline ovarian tumors were not able to enroll. Moreover, those with primary platinum-refractory disease were not eligible to participate.
The primary end point of the study is the confirmed investigator-assessed ORR, and key secondary end points included DOR, safety, progression-free survival, overall survival, and CA-125 response.
Furthermore, SORAYA was designed to rule out a 12% ORR. This is based on expected outcomes with single-agent chemotherapy from the phase 3 AURELIA trial (NCT00976911), which examined the combination of bevacizumab plus chemotherapy in patients with platinum-resistant ovarian cancer who had received up to 2 prior lines of therapy.
Among the 106 patients enrolled on the SORAYA study, the median number of prior lines of therapy was 3 (range, 1-4). Moreover, 51% of patients had received 3 prior lines of therapy, and 48% had received 1 or 2. All patients enrolled on the study received prior treatment with bevacizumab, and 48% of patients received prior treatment with a PARP inhibitor.
As of the data cutoff on November 16, 2021, the median follow-up was 8.1 months.
In terms of safety, mirvetuximab soravtansine was found to be well-tolerated, with a safety profile consistent with what has been observed in prior studies with the agent. Dose reductions due to treatment-related adverse effects (TRAEs) occurred in 19% of patients, dose delays due to TRAEs occurred in 32% of patients, and treatment discontinuations due to TRAEs occurred in 7% of patients. The most frequent TRAEs reported were blurred vision (41% all grade; 6% grade 3 or higher), keratopathy (35% all grade; 9% grade 3 or higher), and nausea (29% all grade; 0% grade 3 or higher).
“These data have the potential to be transformative for ovarian cancer patients and their physicians,” Ursula Matulonis, MD, co-principal investigator, chief of the Division of Gynecologic Oncology at the Dana-Farber Cancer Institute, and professor of medicine at Harvard Medical School, said in a press release. “In the platinum-resistant setting and particularly in later-line treated patients, response rates with available therapy are in the single digits with significant toxicities. With an ORR above 30%, a duration of response of around six months, and a treatment-related discontinuation rate below 10%, mirvetuximab shows impressive activity and tolerability for patients with platinum-resistant ovarian cancer. If approved, mirvetuximab will become a critical therapeutic option for patients with FRα-high ovarian cancer.” Submission of a biologics license application for mirvetuximab soravtansine in this patient population remains on track for the first quarter of 2022.