Epithelial ovarian cancer (EOC) is the most lethal of the gynecologic
malignancies, largely due to the advanced stage at diagnosis in most patients. Standard treatment for EOC is surgical debulking followed by
platinum-based
chemotherapy. While the majority of
ovarian cancer patients will respond to initial
chemotherapy, most will ultimately relapse. The major focus of current clinical trials for treatment of recurrent
ovarian cancer is the use of targeted
biologic agents.
Folate receptor alpha (FRα) is upregulated in majority of EOC and correlated with
tumor stage and grade. It is hypothesized that the presence of overexpressed FRα correlates with the propagation rate of the
tumors. FRα is largely absent from normal tissue, making it an attractive therapeutic target.
Farletuzumab (MORAb-003), a humanized
monoclonal antibody against FRα, has shown antitumor activity in preclinical xenograft models. A Phase 1 dose escalation study did not demonstrate dose-limiting toxicities, or severe adverse effects. A phase 2 efficacy and safety study of
farletuzumab with
carboplatin and
taxane in patients with
platinum-sensitive EOC in first relapse, have shown an improved response rate and time to progression compared with historical controls. Recently, preliminary safety data from a phase 1 trial reported that the combination of
farletuzumab,
carboplatin and
PLD has an acceptable safety profile in patients with
platinum- sensitive EOC following first or second relapse. Two randomized, double-blind, placebo-controlled Phase 3 studies with
farletuzumab plus
chemotherapy have been done. A trial of:
farletuzumab with weekly
paclitaxel in
platinum-resistant EOC closed in December 2011 with full report pending. A second trial of
farletuzumab with
carboplatin and
taxane in
platinum-sensitive EOC in first relapse is slated to complete accrual in early 2012. Results from these trials will help define the role of
farletuzumab in EOC.