MIRASOL: A randomized, open-label, phase 3 study of mirvetuximab soravtansine vs. investigator’s choice of chemotherapy in advanced high-grade epithelial ovarian, primary peritoneal, or fallopian tube cancers with high folate-alpha (FRα) expression (297)

Abstract

Objectives: Elevated FRα expression is a characteristic of epithelial ovarian cancer (EOC), thereby providing an attractive candidate for targeted therapeutic approaches. Mirvetuximab soravtansine is an antibody-drug conjugate (ADC) comprising an FRα-binding antibody, cleavable linker, and the maytansinoid DM4, a potent tubulin-targeting agent that has consistently shown clinically meaningful single-agent activity, along with favorable tolerability, in patients with high FRα expressing tumors (Moore ESMO 2019). Methods: MIRASOL is a randomized phase III study designed to evaluate the efficacy of mirvetuximab soravtansine compared with that of standard-of-care chemotherapy in adult patients with platinum-resistant EOC (including primary peritoneal cancer or fallopian tube cancer). Confirmation of high FRα positivity by immunohistochemistry using the Ventana FOLR1CDx Assay (high expression; ≥ 75% of cells with PS2+ staining intensity) and 1-3 prior lines of therapy are required for inclusion. MIRASOL is designed to randomize 430 patients, 1:1 to Arm 1 (intravenous mirvetuximab soravtansine at a dose of 6 mg/kg, calculated using adjusted ideal body weight, on Day 1 of a 21-day cycle) or Arm 2 (investigators’ choice chemotherapy: paclitaxel, pegylated liposomal doxorubicin, or topotecan). The primary efficacy endpoint is progression-free survival by investigator, and secondary endpoints include objective response rate, quality of life, overall survival, and safety and tolerability. MIRASOL (GOG 3045/ENGOT-ov55) is a global study that opened for enrollment in December 2019. Clinical trial information: NCT04209855. Objectives: Elevated FRα expression is a characteristic of epithelial ovarian cancer (EOC), thereby providing an attractive candidate for targeted therapeutic approaches. Mirvetuximab soravtansine is an antibody-drug conjugate (ADC) comprising an FRα-binding antibody, cleavable linker, and the maytansinoid DM4, a potent tubulin-targeting agent that has consistently shown clinically meaningful single-agent activity, along with favorable tolerability, in patients with high FRα expressing tumors (Moore ESMO 2019). Methods: MIRASOL is a randomized phase III study designed to evaluate the efficacy of mirvetuximab soravtansine compared with that of standard-of-care chemotherapy in adult patients with platinum-resistant EOC (including primary peritoneal cancer or fallopian tube cancer). Confirmation of high FRα positivity by immunohistochemistry using the Ventana FOLR1CDx Assay (high expression; ≥ 75% of cells with PS2+ staining intensity) and 1-3 prior lines of therapy are required for inclusion. MIRASOL is designed to randomize 430 patients, 1:1 to Arm 1 (intravenous mirvetuximab soravtansine at a dose of 6 mg/kg, calculated using adjusted ideal body weight, on Day 1 of a 21-day cycle) or Arm 2 (investigators’ choice chemotherapy: paclitaxel, pegylated liposomal doxorubicin, or topotecan). The primary efficacy endpoint is progression-free survival by investigator, and secondary endpoints include objective response rate, quality of life, overall survival, and safety and tolerability. MIRASOL (GOG 3045/ENGOT-ov55) is a global study that opened for enrollment in December 2019. Clinical trial information: NCT04209855.