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BIW-8962 is a monoclonal antibody to GM2 ganglioside that shows pre-clinical activity towards lung cancer cell lines and in an animal model bearing small-cell lung cancer (SCLC) xenografts. In phase I, patients (N=16) with advanced, recurrent lung cancer received BIW-8962 (1-10 mg/kg) intravenously every 3 weeks. There were no dose-limiting toxicities and the maximum tolerated dose was not established. The highest dose (10 mg/kg) was administered to patients with advanced, recurrent SCLC (N=21) in phase II. The phase II study was prematurely terminated due to lack of efficacy. Objective response rate was 5% (95% CI: 0.1-24.9%) in the efficacy evaluable population (N=20). One patient showed a durable partial response and there were a few with stable disease, which was generally not durable. No pattern of consistent toxicity was observed across the phases: there were no treatment-related adverse events (AEs) grade ? 3, serious AEs, AEs leading to discontinuation of BIW-8962, or deaths. Exploratory analysis of circulating tumor cells and other potentially predictive orpharmacodynamic markers did not reveal any results consistent with an effect from BIW-8962. Given the complete lack of response in the study population, further development of BIW- 8962 has been discontinued. The reason for the lack of clinical activity with BIW-8962 is unknown. It is hoped that the negative findings of this study will contribute to other investigations of GM2 as a therapeutic target, possibly by combination therapy, and of alternative tumor markers in patients with SCLC.
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