PICCOLO: An open-label, single arm, phase 2 study of mirvetuximab soravtansine in recurrent platinum sensitive, high-grade epithelial ovarian, primary peritoneal, or fallopian tube cancers with high folate-alpha (FRα) expression (300)

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: PICCOLO is a single-arm, phase II study designed to evaluate the efficacy of mirvetuximab soravtansine in adult patients with recurrent platinum-sensitive EOC (including primary peritoneal cancer, or fallopian tube cancer) who would be, in the opinion of the investigator, candidates for a non-platinum, single-agent therapy for their next line of therapy. Confirmation of high FRα positivity by immunohistochemistry using the Ventana FOLR1CDx Assay (high expression; ≥ 75% of cells with PS2+ staining intensity) and two prior lines of platinum-based therapy are required for inclusion. Patients with a documented platinum allergy require only one prior line of platinum. PICCOLO will enroll 75 patients who will receive intravenous mirvetuximab soravtansine at a dose of 6 mg/kg, calculated using adjusted ideal body weight, on Day 1 of a 21-day cycle. The primary efficacy endpoint is objective response rate (ORR; by investigator) and secondary endpoints include duration of response, progression-free survival, overall survival, CA-125 response, and safety and tolerability. PICCOLO is a global study that opened for enrollment in August 2021. Clinical trial information: NCT05041257. 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: PICCOLO is a single-arm, phase II study designed to evaluate the efficacy of mirvetuximab soravtansine in adult patients with recurrent platinum-sensitive EOC (including primary peritoneal cancer, or fallopian tube cancer) who would be, in the opinion of the investigator, candidates for a non-platinum, single-agent therapy for their next line of therapy. Confirmation of high FRα positivity by immunohistochemistry using the Ventana FOLR1CDx Assay (high expression; ≥ 75% of cells with PS2+ staining intensity) and two prior lines of platinum-based therapy are required for inclusion. Patients with a documented platinum allergy require only one prior line of platinum. PICCOLO will enroll 75 patients who will receive intravenous mirvetuximab soravtansine at a dose of 6 mg/kg, calculated using adjusted ideal body weight, on Day 1 of a 21-day cycle. The primary efficacy endpoint is objective response rate (ORR; by investigator) and secondary endpoints include duration of response, progression-free survival, overall survival, CA-125 response, and safety and tolerability. PICCOLO is a global study that opened for enrollment in August 2021. Clinical trial information: NCT05041257.