Farletuzumab (a monoclonal antibody against folate receptor alpha) in relapsed platinum-sensitive ovarian cancer

- Complete or partial ORR was 75% with combination therapy.
- Response rate among subjects with first progression-free interval < 12 months (75%) was comparable to subjects with progression-free interval ≥ 12 (84%).
- In 21% of evaluable subjects, second progression-free interval was longer than first progression-free interval.

ObjectiveFarletuzumab is a humanized monoclonal antibody to folate receptor-α, which is over-expressed in most epithelial ovarian cancers but largely absent on normal tissue. We evaluated clinical activity of farletuzumab, alone and combined with chemotherapy, in women with first-relapse, platinum-sensitive ovarian, fallopian tube and primary peritoneal cancers.MethodsFifty-four eligible subjects received open-label farletuzumab weekly, single agent or combined with carboplatin (AUC5-6) and taxane (paclitaxel 175 mg/m2 or docetaxel 75 mg/m2), every 21 days for 6 cycles, followed by farletuzumab maintenance until progression. Twenty-eight subjects with asymptomatic CA125 relapse received single-agent farletuzumab and could receive platinum/taxane chemotherapy plus farletuzumab after single-agent progression. Twenty-six subjects with symptomatic relapse entered the combination arm directly; 21 subjects entered after single agent. Primary endpoints included normalized CA125 and Overall Response Rate (ORR). Duration of each subject's second progression-free interval (PFI2) was compared with her own first response interval (PFI1).ResultsFarletuzumab was well-tolerated as single agent, without additive toxicity when administered with chemotherapy. Of 47 subjects who received farletuzumab with chemotherapy, 38 (80.9%) normalized CA125. In 9/42 (21%) evaluable subjects, PFI2 was ≥ PFI1, better than the historical rate (3%). There was a high response rate among subjects with PFI1 < 12 months (75%), comparable to that in subjects with PFI1 ≥ 12 months (84%). Complete or partial ORR was 75% with combination therapy.ConclusionBased on this study, farletuzumab with carboplatin and taxane may enhance the response rate and duration of response in platinum-sensitive ovarian cancer patients with first relapse after remission of 6-18 months.