Farletuzumab in epithelial ovarian carcinoma

IMPORTANCE OF THE FIELD: Ovarian cancer is the leading cause of death from a gynecologic malignancy. Recurrence is both common and lethal, necessitating the development of novel targeted therapies. Farletuzumab (MORAb-003) is a humanized mAb with high affinity for folate receptor alpha (FRalpha), a 38 kDa GPI-anchored protein that is overexpressed in 90% of epithelial ovarian cancers. AREAS COVERED IN THIS REVIEW: Preclinical and clinical trials, published or presented at national meetings from 2006 to the present, are presented in this review. WHAT THE READER WILL GAIN: Preclinical studies have demonstrated robust antibody-dependent cellular cytotoxicity and complement-dependent cytotoxicity in vitro, inhibition of tumor growth in ovarian tumor xenografts and a safe toxicology profile in non-human primates. Phase I and II studies have demonstrated single agent and combination therapy efficacy with minimal drug-specific toxicity. The Phase III development plan in ovarian cancer patients includes combination chemotherapy studies in both platinum-sensitive (recently launched) and platinum-resistant (planned) recurrent disease. TAKE HOME MESSAGE: FRalpha is overexpressed in ovarian cancers but largely absent from normal tissue, making it an attractive therapeutic target. Farletuzumab is a novel inhibitor of FRalpha and has shown clinical efficacy in early phase trials.