A multi-institutional phase II study of BMS-182248-01 (BR96-doxorubicin conjugate) administered every 21 days in patients with advanced gastric adenocarcinoma

PURPOSE: High levels (> 200,000 molecules per carcinoma cell) of the Lewis(Y) antigen are expressed on the surface of most (> 75%) gastric carcinomas. The BMS-182248-01 is a chimeric variant of anti-Lewis(Y) monoclonal antibody that is conjugated with doxorubicin. In a phase I study, BMS-182248-01 resulted in a partial response in a patient with gastric carcinoma. We, therefore, conducted a multi-institutional phase II study of BMS-182248-01 in patients with advanced gastric carcinoma. METHODS AND PATIENTS: Only patients with evidence of Lewis(Y) antigen by immunohistochemical method on their gastric carcinoma were treated. Patients with unresectable gastric adenocarcinoma were eligible. Patients had to have adequate liver, renal, and marrow functions. Written consent was obtained from all patients. All patients were hospitalized. BMS-182248-01 was administered at the starting dose of 700 mg/m² I.V. over 24 hours on day 1 every 3 weeks. RESULTS: Fifteen patients were enrolled. There were 10 men and 5 women. The median age at enrollment was 56 years, with ages ranging from 34 to 80 years. No objective responses were observed. Five patients had disease stabilization. The remaining 10 patients progressed on study. Rapidly reversible gastrointestinal toxicity, primarily nausea and emesis, was predominant. There was no neutropenia, thrombocytopenia, or cardiomyopathy. CONCLUSIONS: Although BMS-182248-01 represents a novel approach of monoclonal antibody conjugated with an active chemotherapy agent, delivered intracellularly, it was ineffective in patients with gastric carcinoma whose tumors carried Lewis(Y) antigen.