Phase I Trial of the Anti–Lewis Y Drug Immunoconjugate BR96-Doxorubicin in Patients With Lewis Y–Expressing Epithelial Tumors

PURPOSE: We conducted a phase I clinical trial of BR96-Doxorubicin (BR96-Dox), a chimeric anti–Lewis Y (LeY) monoclonal antibody conjugated to doxorubicin, in patients whose tumors expressed the LeY antigen. The study aimed to determine the toxicity, maximum-tolerated dose, pharmacokinetics, and immunogenicity of BR96-Dox. PATIENTS AND METHODS: This was a phase I dose escalation study. BR96-Dox was initially administered alone as a 2-hour infusion every 3 weeks. The occurrence of gastrointestinal (GI) toxicity necessitated the administration of BR96-Dox as a continuous infusion over 24 hours and use of antiemetics and antigastritis premedication. Patients experiencing severe GI toxicity underwent GI endoscopy. All patients underwent restaging after two cycles. RESULTS: A total of 66 patients predominantly with metastatic colon and breast cancer were enrolled onto the study. The most common side effects were GI toxicity, fever, and elevation of pancreatic lipase. At higher doses, BR96-Dox was associated wi...