Farletuzumab in epithelial ovarian carcinoma.
BACKGROUND
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.


METHODS
Preclinical and clinical trials, published or presented at national meetings from 2006 to the present, are presented in this review.


RESULTS
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.


CONCLUSIONS
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.
Spannuth
Whitney A
WA
University of Texas MD Anderson Cancer Center, Department of Gynecologic Oncology, 1155 Herman Pressler Drive, Houston, TX 77030-3271, USA.
Sood
Anil K
AK
Coleman
Robert L
RL
D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D009375:Neoplasms, Glandular and Epithelial / Q000188:drug therapy*; D010051:Ovarian Neoplasms / Q000188:drug therapy*; D016896:Treatment Outcome
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; C527484:farletuzumab