Assessment of mirvetuximab soravtansine immunogenicity in patients with folate receptor alpha-positive ovarian cancer

Aim: The aim of this research was to evaluate the immunogenicity of mirvetuximab soravtansine (MIRV), an antibody-drug conjugate in patients with folate receptor alpha-positive ovarian cancer across four clinical studies. Materials & methods: An assay was developed and validated for the detection of antidrug antibodies (ADAs) against MIRV. A cell-based method was also developed and validated for the detection of neutralizing anti-MIRV antibodies (NAbs). Both ADAs and NAbs were assessed across four clinical studies in 734 patients. Results: Across studies, MIRV demonstrated low immunogenicity with 7.8% of patients with treatment-emergent ADAs, 7.2% with treatment-unaffected ADAs, and 0.5% with treatment-enhanced ADAs. MIRV trough concentrations were comparable in ADA-negative and ADA-positive individuals. Limited data suggest that MIRV ADAs may be associated with decreased efficacy. Due to the very limited number of NAb-positive individuals, no conclusions could be drawn on the effect of NAb on efficacy. Conclusion: Both the validation tests and the data from the MIRV clinical studies demonstrated that these assays were suitable and reliable for the detection of MIRV ADAs and NAbs. These validated assays will continue to be used to monitor MIRV immunogenicity in future clinical trials. Mirvetuximab soravtansine (MIRV) is a new drug of cancer treatment that targets a protein called folate receptor alpha, which is often found in certain ovarian cancers that do not respond to platinum-based therapies. To check if patients’ immune systems react to this drug, we developed tests to look for antibodies that may form against MIRV. These antibodies can affect how well the drug works. The study looked at 734 patients in four different clinical trials. It found that MIRV triggered an immune response in only a small number of patients – 7.8% developed new antibodies after starting treatment. However, most of these antibodies did not seem to impact the effectiveness of the drug, and patients with or without antibodies had similar levels of the drug in their bodies. Some data hinted that having antibodies might slightly reduce how well the drug works, but there were not enough patients who developed these antibodies to be certain. Another test was done to check if certain antibodies blocked MIRV from working, but very few patients (31 out of 734) had these, so no conclusions could be made. Overall, the tests were shown to work well and will continue to be used in future