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 (FR alpha), 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 anti body-de pendent 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: FR alpha is overexpressed in ovarian cancers but largely absent from normal tissue, making it an attractive therapeutic target. Farletuzumab is a novel inhibitor of FR alpha and has shown clinical efficacy in early phase trials.