The exploration of mirvetuximab soravtansine as a potentially efficacious treatment in patients with advanced, high-grade, platinum-resistant epithelial ovarian, primary peritoneal, or fallopian tube cancers with high folate receptor–alpha expression continues with the ongoing, single-arm, phase 3 SORAYA trial.
The exploration of mirvetuximab soravtansine as a potentially efficacious treatment in patients with advanced, high-grade, platinum-resistant epithelial ovarian, primary peritoneal, or fallopian tube cancers with high folate receptor–alpha (FRα) expression continues with the ongoing, single-arm, phase 3 SORAYA (NCT04296890) trial.1
The study, which was presented as a trial in progress during the 2021 SGO Virtual Annual Meeting on Women’s Cancer, is being led by Ursula Matulonis, MD, chief of the Division of Gynecologic Oncology, at Dana-Farber Cancer Institute.
Though there have been advances with PARP inhibitors and antiangiogenic drugs in patients with newly diagnosed ovarian cancer, there are still unmet needs for therapies to target patients who have recurrent disease.
Mirvetuximab soravtansine, which is an antibody-drug conjugate (ADC) that includes a FRα-binding antibody, cleavable linker, and the maytansinoid DM4, a potent tubulin-targeting agent, has shown intriguing activity and tolerability as a monotherapy in FRα–expressing ovarian cancer.
In the single-arm SORAYA study, which is actively enrolling, investigators anticipate enrolling approximately 110 patients with platinum-resistant disease with a platinum-free interval (PFI) of less than 6 months and are deemed FRα–high by PS2+ scoring (≥75% PS2+). Prior treatment with bevacizumab (Avastin) is required and PARP inhibitions are permitted, and patients overall can have undergone 1 to 3 prior lines of therapy and must have progressed on or after their most recent line of therapy.
Additionally, those with BRCA mutations are permitted. Patients with platinum-refractory disease, consisting of a PFI of less than 3 months, are excluded.
Mirvetuximab soravtansine is administered at 6 mg/kg that is adjusted using ideal body weight once every 3 weeks. The primary end point is confirmed, investigator-assessed ORR in patients with platinum-resistant ovarian cancer as well as those with high FRα expression. Secondary outcome measures were duration of response (DOR) in the overall and FRα–high subgroup, as well treatment-emergent adverse events, CA-125 response via Gynecological Cancer Intergroup criteria, progression-free survival (PFS), and overall survival.
Responses will be evaluated by the investigator via RECIST v1.1 criteria; additionally, CT/MRI scans will be collected for sensitivity analyses by blinded independent central review.
Mirvetuximab soravtansine previously was evaluated in the phase 3 FORWARD I trial. In a comprehensive analysis of the study, results showed that the ADC had a favorable benefit-risk profile in a prespecified subset of patients with FRα—positive ovarian cancer.2,3
In the open-label, FORWARD I study, 366 patients were randomized 2:1 to receive either mirvetuximab soravtansine at 6 mg/kg adjusted ideal body weight or physician’s choice of single-agent chemotherapy, which comprised pegylated liposomal doxorubicin, topotecan, or weekly paclitaxel.
Although the median PFS was longer with mirvetuximab soravtansine in the prespecified high FRα—positive subgroup at 4.8 months vs 3.3 months, respectively (HR, 0.69; P = .049), it was not enough to reach statistical significance as per a prespecified statistical analysis plan.
In the overall study population, there were no significant differences in median PFS, at 4.1 months with mirvetuximab soravtansine and 4.4 months for chemotherapy (HR, 0.98; P = .897).
The confirmed ORR in the overall population was 22% for mirvetuximab soravtansine and 12% for chemotherapy (P = .15).
In the prespecified high FRα subgroup (n = 218), the confirmed ORRs were 24% and 10% for mirvetuximab soravtansine and chemotherapy, respectively (P = .014).
The agent also has been evaluated in combination with bevacizumab in the platinum-resistant, recurrent ovarian cancer setting. In a phase 1b trial, data showed that the ADC led to an ORR of 39%, including 5 complete responses and 21 partial responses. The median PFS was 6.9 months.
In those with FRα expression, the ORR was 56%, the median PFS was 9.9 months, and the median DOR was 12 months.