Efficacy and Safety of Mirvetuximab Soravtansine in Patients With Platinum-Resistant Ovarian Cancer With High Folate Receptor Alpha Expression: Results From the SORAYA Study

Approximately 80% of patients with ovarian cancer experience recurrence after platinum-based chemotherapy, and unfortunately nearly all will eventually develop platinum-resistant ovarian cancer (PROC). Treatment in this setting consists of nonplatinum chemotherapy with or without bevacizumab; however, each successive line of therapy in PROC is associated with progressively lower response rates. Mirvetuximab soravtansine (MIRV) is an antibody-drug conjugate composed of an antifolate receptor alpha (FRa) monoclonal antibody and the maytansinoid DM4 payload, a tubulin-targeting antimitotic agent. A phase III evaluation of MIRV in PROC did not meet its primary end point of progression-free survival; however, it had a favorable safety profile compared with chemotherapy and some evidence that higher FRa expression may lead to greater response. The SORAYA study was a single-arm phase II study evaluating the safety and efficacy of MIRVin patients with FRa-high, platinum-resistant, advanced high-grade serous ovarian cancer. Female adults with a diagnosis of platinum-resistant, highFRa, high-grade serous ovarian cancer, primary peritoneal cancer, or fallopian tube cancer were considered eligible. Patients were enrolled at 39 sites in 8 countries and received single-agent MIRV at 6 mg/kg administered intravenous once every 3 weeks. The primary study end point was objective response rate (ORR) by RECIST 1.1 criteria, and the secondary end point was duration of response (DOR), defined as the time from initial complete or partial response until progressive disease. The final safety and efficacy populations of the study were 106 and 105, respectively. Notably, 36% of patients screened were found to have high tumor FRa expression. The primary end point was met with an ORR of 32.4% (95% confidence interval, 23.6-42.2; P < 0.0001), including 5 patients with a complete response and 29 achieving a partial response. Tumor reduction occurred in 71.4% of patients, and the median progression-free survival was 4.3 months (95% confidence interval, 3.7-5.2). The safety population included patients who received at least 1 MIRV dose. Treatment-related adverse events were experienced by 86% of patients, with 28% experiencing at least 1 grade 3 event and 1% experiencing a grade 4 event. Treatment-related grade 4 keratopathy occurred in a single patient, which resolved to grade 0 in 15 days with complete resolution to baseline. A total of 55 (52%) patients experienced any-grade blurred vision or keratopathy, with 12 patients (11%) requiring a dose reduction and a single patient requiring discontinuation due to an ocular adverse event. Serious grade >3 treatmentrelated adverse events were reported in 9% of patients and led to dose delay in 33% of patients and reduction in 20%. The results of the SORAYA study show that MIRV monotherapy elicited high ORRs, durable responses, and a tolerable safety profile in patients with high-FRa PROC.