Phase III, randomized trial of mirvetuximab soravtansine versus chemotherapy in patients with platinum-resistant ovarian cancer: primary analysis of FORWARD I.

ABSTRACT Background Mirvetuximab soravtansine is an antibody-drug conjugate comprising a folate receptor-alpha (FRα)-binding antibody, cleavable linker, and the maytansinoid DM4, a potent tubulin-targeting agent. The randomized, open label, phase III study FORWARD I compared mirvetuximab soravtansine and investigator’s choice chemotherapy in patients with platinum-resistant epithelial ovarian cancer (EOC). Patients and methods Eligible patients with 1-3 prior lines of therapy and whose tumors were positive for FRα expression were randomly assigned, in a 2:1 ratio, to receive mirvetuximab soravtansine (6 mg/kg, adjusted ideal body weight) or chemotherapy (paclitaxel, pegylated liposomal doxorubicin, or topotecan). The primary endpoint was progression-free survival (PFS, RECIST version 1.1, blinded independent central review) in the intention-to-treat (ITT) population and in the prespecified FRα high population. Results A total of 366 patients were randomized; 243 received mirvetuximab soravtansine and 109 received chemotherapy. The primary endpoint, PFS, did not reach statistical significance in either the ITT (hazard ratio [HR], 0.98, P = 0.897) or the FRα high population (HR, 0.69, P = 0.049). Superior outcomes for mirvetuximab soravtansine over chemotherapy were observed in all secondary endpoints in the FRα high population including improved objective response rate (24% v 10%), CA-125 responses (53% v 25%), and patient reported outcomes (27% v 13%). Fewer treatment-related grade 3 or higher adverse events (25.1% v 44.0%), and fewer events leading to dose reduction (19.8% v 30.3%) and treatment discontinuation (4.5% v 8.3%) were seen with mirvetuximab soravtansine compared to chemotherapy. Conclusions In patients with platinum-resistant EOC, mirvetuximab soravtansine did not result in a significant improvement in PFS compared with chemotherapy. Secondary endpoints consistently favored mirvetuximab soravtansine, particularly in patients with high FRα expression. Mirvetuximab soravtansine showed a differentiated and more manageable safety profile than chemotherapy.