FORWARD I (GOG 3011): A randomized phase 3 study to evaluate the safety and efficacy of mirvetuximab soravtansine (IMGN853) versus chemotherapy in adults with folate receptor alpha (FRα)-positive, platinum-resistant epithelial ovarian cancer (EOC), primary peritoneal cancer, or primary fallopian tube cancer.

Abstract

TPS5607 Background: Elevated FRα expression is characteristic of a number of solid tumors, including EOC, thereby providing an attractive candidate for targeted therapeutic approaches. Mirvetuximab soravtansine is an antibody-drug conjugate (ADC), comprising a FRα-binding antibody linked to the tubulin-disrupting maytansinoid DM4, that has shown single agent clinical activity and a favorable safety profile in an ongoing, first-in-human phase 1 trial (NCT01609556). Methods: FORWARD I is a randomized phase 3 study designed to evaluate the efficacy of mirvetuximab soravtansine compared with that of standard-of-care chemotherapy in adult patients with platinum-resistant EOC, primary peritoneal cancer, or fallopian tube cancer. Confirmation of FRα positivity by immunohistochemistry (medium or high expression; ≥ 50% of cells with at least moderate staining intensity) and ≤ 3 prior lines of therapy are required for inclusion. A maximum of 333 patients are expected to be recruited. Patients will be randomized 2:1 to Arm 1 (intravenous mirvetuximab soravtansine at a dose of 6.0 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 (PFS; by blinded independent central review) and secondary endpoints include objective response rate, quality of life, overall survival, safety and tolerability, and duration of response. The first patient was enrolled in January 2017. Clinical trial information: NCT02631876.