Elevated FRa expression is characteristic of a number of solid tumors, including epithelial ovarian cancer (EOC), thus providing an attractive candidate for targeted therapeutic approaches. Mirvetuximab soravtansine is an antibody-drug conjugate (ADC) comprising a potent cytotoxic effector molecule, the tubulin-disrupting maytansinoid DM4, linked to a humanized anti-FRa monoclonal antibody. In a recently completed phase 1 trial in heavily pre-treated ovarian cancer patients, mirvetuximab soravtansine showed a favorable safety profile and promising single-agent clinical activity.
FORWARD I is a randomized phase 3 study designed to evaluate the efficacy of mirvetuximab soravtansine compared to standard-of-care chemotherapy in adult patients with platinum-resistant EOC, primary peritoneal cancer, or fallopian tube cancer. Inclusion criteria include confirmation of tumor FRa positivity by immunohistochemistry (medium or high receptor expression; ≥ 50% of cells with at least moderate staining intensity) and ≤ 3 prior lines of therapy. A total of 333 patients are expected to be recruited, who will be randomized 2:1 to mirvetuximab soravtansine dosed intravenously at 6.0 mg/kg, calculated according to adjusted ideal body weight, on Day 1 of a 21-day cycle or investigators’ choice chemotherapy (paclitaxel, pegylated liposomal doxorubicin, or topotecan). Progression-free survival (PFS; assessed by blinded independent central review) is the primary efficacy endpoint; secondary endpoints include objective response rate, quality of life, overall survival, safety and tolerability, and duration of response. The first patient enrolled in January 2017.
Clinical trial identification
Legal entity responsible for the study
K.N. Moore, I. Vergote: Advisory board service for ImmunoGen, Inc. K. Malek: Employed by ImmunoGen, Inc. M.J. Birrer: Advisory board service for ImmunoGen, Inc. All other authors have declared no conflicts of interest.