Phase II trial of humanized anti-Lewis Y monoclonal antibody for advanced hormone receptor-positive breast cancer that progressed following endocrine therapy.

OBJECTIVES: The Lewis-Y antigen is expressed in 44%-90% of breast cancers (BCs). The expression of the antigen in carcinoma tissue differs from that in normal tissues. This study aimed to evaluate the clinical benefit of the humanized anti-Lewis Y monoclonal antibody, hu3S193, in advanced hormone receptor-positive and Lewis Y-positive BC after administration of endocrine therapy (ET). METHODS: A single-arm phase II study was conducted in seven centers. Patients with advanced hormone receptor-positive BC who failed first-line ET were included. The inclusion criterion was the observation of tumoral expression of the Lewis Y antigen during immunohistochemistry. The treatment comprised hu3S193 antibody administration at weekly intravenous doses of 20 mg/m2 for 8-week cycles. The primary endpoint was the clinical benefit rate. ClinicalTrials.gov NCT01370239. RESULTS: The study stopped accrual following an unplanned interim analysis as the hu3S193 antibody lacked sufficient activity to justify continuation of the study. Twenty-two patients were enrolled, of whom 21 were included in the efficacy analysis. The clinical benefit rate was 19%, with four patients presenting with stable disease after 24 weeks. One patient with prolonged stable disease received medication for over 2 years. No partial or complete responses were observed. The median time to progression and overall survival was 5.4 and 37.5 months, respectively. CONCLUSIONS: The humanized anti-Lewis Y monoclonal antibody, hu3S193, exhibited insufficient activity in this cohort. However, the possibility of activity in a more strictly selected subgroup of patients with higher levels of Lewis Y tumoral expression cannot be overlooked.