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/m2) 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/m2). 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/m2. The maximum tolerated dose (MTD) was established at 40 mg/m2 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/m2 for course 1 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/m2 cohort had stable disease. CONCLUSIONS: An MTD of 40 mg/m2 without premedication was established for KW-2871, with urticaria being the most common side-effect and dose-limiting anaphylactoid infusion reactions.
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/m2) 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/m2). 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/m2. The maximum tolerated dose (MTD) was established at 40 mg/m2 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/m2 for course 1 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/m2 cohort had stable disease. CONCLUSIONS: An MTD of 40 mg/m2 without premedication was established for KW-2871, with urticaria being the most common side-effect and dose-limiting anaphylactoid infusion reactions.
Authors: Tonya J Webb; Xiangming Li; Robert L Giuntoli; Pablo H H Lopez; Christoph Heuser; Ronald L Schnaar; Moriya Tsuji; Christian Kurts; Mathias Oelke; Jonathan P Schneck Journal: Cancer Res Date: 2012-05-30 Impact factor: 12.701
Authors: Mireille Vankemmelbeke; Richard S McIntosh; Jia Xin Chua; Thomas Kirk; Ian Daniels; Marilena Patsalidou; Robert Moss; Tina Parsons; David Scott; Gemma Harris; Judith M Ramage; Ian Spendlove; Lindy G Durrant Journal: Cancer Res Date: 2020-06-12 Impact factor: 12.701
Authors: Irene Y Cheung; Nai-Kong V Cheung; Shakeel Modak; Audrey Mauguen; Yi Feng; Ellen Basu; Stephen S Roberts; Govind Ragupathi; Brian H Kushner Journal: J Clin Oncol Date: 2020-12-16 Impact factor: 44.544