A phase I study of an anti-GD3 monoclonal antibody, KW-2871, in patients with metastatic melanoma

Purpose: KW-2871 (IgG1 kappa chimeric antibody) targets GD3, which is upregulated in melanomas. We conducted a phase I trial of KW-2871 in patients with metastatic melanoma. Methods: Seventeen (17) patients were enrolled and received an initial test dose (10 mg/m(2)) intravenously. Two (2) weeks later, patients were stratified into 4 cohorts to receive 4 doses of KW-2871 (infused over 1 hour) at 2-week intervals (20, 40, 60, and 80 mg/m(2)). No premedications were administered for the test or first therapeutic doses. Results: Dose-limiting toxicities were Grade 3 laryngospasm and chest tightness with the initial therapeutic infusion at doses of 80 and 60 mg/m(2). The maximum tolerated dose (MTD) was established at 40 mg/m(2) of KW2871. The most common side-effect was urticaria (Grades 1-3) in 16 of 16 patients during an initial therapeutic infusion without premedication. The mean terminal half-life, clearance, and area under the concentration-time curve (AUC(0-t)) at a dose of 40 mg/m(2) for course I were 146 +/- 31 hours, 28 +/- 6 ml/hour, and 1922 +/- 491 mcg*hour/mL, respectively. Anti-human chimeric antibody was not detected. Two (2) patients in the 40 mg/m(2) cohort had stable disease. Conclusions: An MTD of 40 mg/m(2) without premedication was established for KW-2871, with urticaria being the most common side-effect and dose-limiting anaphylactoid infusion reactions.