October 2, 2009 (Berlin, Germany) — Although the data are early, farletuzumab appears to increase the duration of second remission in women with relapsed ovarian cancer. When combined with platinum and taxane, the objective response rate was significantly higher than that from historic data for platinum/taxane regimens alone.

According to the results of the open-label phase 2 trial, which were presented here at the 15th Congress of the European CanCer Organization and the 34th European Society for Medical Oncology Multidisciplinary Congress, 73.5% of patients using combination therapy with farletuzumab achieved objective response. Median progression-free survival in this group was 10.3 months.

Farletuzumab is an investigational product under development by Morphotek. It is a humanized monoclonal antibody to folate receptor alpha, which is overexpressed in most epithelial ovarian cancers but largely absent in normal tissue. Efficacy was demonstrated in preclinical xenograft models of ovarian cancer, and activity was demonstrated in antibody-dependent cellular cytotoxicity assays.

In addition, a phase 1 trial conducted using farletuzumab as a single agent showed signs of efficacy, explained lead study author Deborah Armstrong, MD, associate professor of oncology at the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University in Baltimore, Maryland.

"The results of phase 1 trials found that it had a favorable safety profile up to 400 mg/m2 IV given weekly, with 4 doses given," said Dr. Armstrong. "This was the highest dose tested; no maximum tolerated dose was identified. Radiolabelled farletuzumab also demonstrated tumor binding."

Current Study Details

The current study involved 54 patients with ovarian, fallopian tube, or primary peritoneal cancer, with disease that was evaluable by CA125 at baseline. Those with low-volume or symptomatic disease could go on single-agent farletuzumab until progression, whereas patients with symptomatic or large-volume disease continued with their original platinum/taxane regiment with farletuzumab for a target of 6 cycles.

"Patients on single-arm therapy who progressed could cross over, and those who had completed combination therapy could go on a maintenance farletuzumab trial," said Dr. Armstrong.

All patients received farletuzumab 100 mg/m2 weekly, and those in the combination-therapy group received carboplatin AUC 5 or 6 every 21 days for 6 cycles, and either paclitaxel 175 m/m2 over 3 hours or docetaxel 75 mg/m2 every 3 weeks for 6 cycles.

Dr. Armstrong pointed out that the median length of the first progression-free interval was 15.5 months (range, 6.3–29.7). "Approximately one third of patients were in the 6- to 12-month range of progression-free interval, so about a third had relapsed within a fairly short time," she said.

Twenty-eight patients entered the single-agent group and, of this group, 21 continued on to combination therapy. At baseline, 26 patients entered the combination-therapy group, making a total of 47 patients treated with combination therapy. Of this group, 44 were evaluable for response.

Single-Agent Results

A total of 25 patients in the single-agent group completed at least 9 weeks of therapy. At week 7, day 43:

  • 1 patient had more than a 75% decrease in CA125

  • 1 patient had more than a 50% decrease in CA125

  • 3 patients had more than a 25% decrease in CA125

  • 13 patients were unchanged

  • 6 patients had an increase in CA125 levels

  • 1 patient was missing.

"Our summary from single-agent use is that additional studies are needed, and planned, to determine optimal use," said Dr. Armstrong.

Measurable disease using Response Evaluation Criteria in Solid Tumors (RECIST) showed no responses, but there was stable disease in 38.5% of the single-agent cohort and progressive disease in 53.8%; 7.7% of the group was not evaluable.

Combination Trial Results

In the combination group, 39 patients achieved a normal CA125 (88.6%). Of the 5 patients (11.4%) who did not normalize their CA125, 3 achieved a greater than 50% reduction.

Within this group, 4 patients are continuing on in the study and 9 (20.5%) have had a second progression-free survival interval that is longer than their first one.

"A few of the patients had second progression-free intervals that were substantially longer — 2 to 3 times longer than their first ones," she said. In other patients, the intervals were similar.

RECIST data were available for 43 patients (98%), and showed that a complete response was achieved by 7.0%, a partial response was achieved by 62.8%, stable disease was achieved by 23.2%, and disease progression was seen in 7.0%. The overall response rate was 69.8%.

Overall, the treatment regimen was very well tolerated, with infrequent grade 1 or 2 infusion reactions, Dr. Armstrong pointed out. There was no additive toxicity observed in the carboplatin/taxane group, but 5 serious adverse events were observed in 3 patients.

"Compared with historical progression-free intervals, farletuzumab increases the duration of the second progression-free interval when combined with carboplatin and taxane," she concluded. "Single-agent farletuzumab may stabilize disease for an indeterminate time."

Randomized clinic studies are being planned or are underway to test farletuzumab in platinum-sensitive and platinum-resistant relapsed ovarian cancer, Dr. Armstrong added.

The study was funded by Morphotek, the manufacturer of farletuzumab. Dr. Armstrong is an advisory board member for Morphotek, and her employer has received funding in support of research for the study.

15th Congress of the European CanCer Organization (ECCO 15) and the 34th European Society for Medical Oncology (34th ESMO) Multidisciplinary Congress: Abstract 8000. Presented September 24, 2009.

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