Researchers involved in a multicenter Phase II clinical trial have reported that the addition of farletuzumab (MORab-003) to a taxane and a platinum compound increases the response rate in women with platinum-sensitive relapse compared with historical controls. The details of this study were presented at the Joint ECCO 15 – 34^th ESMO Multidisciplinary Congress in Berlin, September 20-24, 2009.[1]

Patients who develop recurrent ovarian cancer more than six months after first-line chemotherapy with platinum and taxane chemotherapy have a good chance of improving with retreatment with the same drugs. The length of time between the completion of first-line chemotherapy and the development of recurrent disease can help determine whether additional treatment with a taxane and platinum will be effective. Over half of patients who develop a recurrence longer than 12 months from initial treatment are likely to improve with further chemotherapy compared with less than half of patients who develop a recurrence between six and 12 months from initial treatment.

The only monoclonal antibody that has been extensively tested in women with recurrent ovarian cancer is Avastin® (bevacizumab), which appears to be effective and reasonably well tolerated. Avastin is a recombinant humanized monoclonal antibody to vascular endothelial growth factor (VEGF).

Farletuzumab (MORAb-003) is a humanized monoclonal antibody directed at folic acid receptor alfa (FRA). Farletuzumab has been shown to have antiproliferative and cytotoxic activities in tumor cells that over express FRA. Phase I studies have suggested significant activity in patients with ovarian cancer, and farletuzumab has been granted orphan status for ovarian and pancreatic cancer by the European Regulatory Agency.

A Phase II open label-study of farletuzumab was presented at the ECCO-ESMO congress. This study measured overall response rate (ORR), duration of second remission, and changes in CA-125 levels following treatment of patients with platinum-sensitive relapse of ovarian cancer. This study was carried out in approximately 20 centers in the United States, Germany, and the Netherlands. Treatment consisted of a taxane, a platinum compound, and farletuzumab. Patients who achieved a complete or partial response received farletuzumab as maintenance therapy.

Preliminary data were available for 41 patients. The overall response rate was 73.5% with a progression-free survival of 10.3 months. Thirty-seven patients (90.2%) had their CA-125 blood levels normalized. In ten of these 37 patients who had normalization of CA-125, the duration of second remission was equal to or longer than duration of the first remission. Farletuzumab did not appear to significantly increase toxicity above that expected from the taxane and platinum regimen.

These authors suggested that farletuzumab increased the overall response rate compared with historical controls receiving a taxane and a platinum compound for platinum-sensitive disease.

Comments: Farletuzumab appears to be a very interesting new drug for the treatment of ovarian cancer. There are currently two ongoing studies; one Phase III study in patients with platinum-sensitive relapse and a Phase II randomized study with weekly taxane in platinum-resistant patients. Several U.S. medical centers are participating in these clinical trials. Details of these studies can be accessed on the Morphotek Web site (www.morphotek.com). 

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