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 Lavis(Y) antige n 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 i s conjugated with doxorubicin. In a phase I study, BMS-182248-01 resulted i n a partial response in a patient with gastric carcinoma. We, therefore, co nducted a multi-institutional phase II study of BMS-182248-01 in patients w ith advanced gastric carcinoma. METHODS AND PATIENTS Only patients with evidence of Lewis(Y) antigen by immunohistochemical meth od an their gastric carcinoma were treated. Patients with unresectable gast ric adenocarcinoma were eligible. Patients had to have adequate liver, rena l, and marrow functions. Written consent was obtained from all patients. AU patients were hospitalized. BMS-182248-01 uas administered at the starting dose of 700 mg/m(2) 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 a ge at enrollment was 56 years, with ags ranging from 34 to 80 years. No obj ective responses were observed. Five patients had disease stabilization. Th e remaining 10 patients progressed on study. Rapidly reversible gastrointes tinal 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 c onjugated with an active chemotherapy agent, delivered intracellularly, it was ineffective in patients with gastric carcinoma whose tumors carried Lew is(Y) antigen.