Phase I safety study of farletuzumab, carboplatin, and pegylated liposomal doxorubicin (PLD) in patients with platinum-sensitive epithelial ovarian cancer (EOC).

Abstract

5062^ Background: Farletuzumab (FAR) is a humanized monoclonal antibody that binds to folate receptor-α, a target which is largely absent in normal epithelium and over-expressed in EOC. A phase I and a phase II study indicate potential utility of FAR in combination with carboplatin/paclitaxel in recurrent platinum sensitive EOC. This study assessed safety and efficacy of FAR in combination with PLD/carboplatin, which has been demonstrated to have greater efficacy than carboplatin/paclitaxel in women with platinum-sensitive EOC. Methods: A multicenter, single-arm study enrolled 15 patients with platinum-sensitive EOC in first or second relapse defined by either CA-125 or RECIST. The primary endpoint is to assess safety of FAR plus PLD/carboplatin in this population. Patients were treated with weekly FAR 2.5 mg/kg plus carboplatin AUC 4-5 and PLD 30 mg/m2 every 4 weeks for 6 cycles, followed by maintenance treatment with single agent FAR until disease progression. Initial dosing of weekly 2.5 mg/kg was later amended to 7.5 mg/kg every 3 weeks. Results: 13 of 15 patients completed 6 cycles of combination therapy; one received a total of 12 cycles of chemotherapy. Two patients progressed during combination therapy: one received 3 cycles, the other 5 cycles. The median number of subsequent single agent maintenance cycles was 8 (range 0-13). No grade 4 toxicities were observed. Of 20 grade 3 toxicities in 14 patients, 3 (1 fatigue; 2 small bowel obstructions in the same patient) were deemed by the investigator to be possibly related to FAR. These events were seen during the combination phase and were deemed by the investigator to be also possibly related to chemotherapy. All patients demonstrated clinical benefit: 1 complete response, 10 partial response and 4 stable disease. 7 patients have come off study, all for disease progression; a median PFS of 11 months was noted. 8 patients remain on study. Conclusions: These preliminary data indicate that the safety profile of FAR in combination with carboplatin and PLD is consistent with that historically recorded for carboplatin and PLD alone. Complete safety profile will be assessed; PK data and final results will be presented.