title: A phase I study of an anti-GD3 monoclonal antibody, KW-2871, in patients with metastatic melanoma.
abstract: OBJECTIVE
  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.affiliation: Department of Medicine, Division of Hematology/Oncology, University of Alabama at Birmingham Comprehensive Cancer Center, Birmingham, AL 35294-3300, USA. Andres.Forero@ccc.uab.edu
authors.forename: Andres
authors.initials: A
authors.lastname: Forero
authors.forename: Jatin
authors.initials: J
authors.lastname: Shah
authors.forename: Ronda
authors.initials: R
authors.lastname: Carlisle
authors.forename: Pierre L
authors.initials: PL
authors.lastname: Triozzi
authors.forename: Albert F
authors.initials: AF
authors.lastname: LoBuglio
authors.forename: Wen-Quan
authors.initials: WQ
authors.lastname: Wang
authors.forename: Matt
authors.initials: M
authors.lastname: Fujimori
authors.forename: Robert M
authors.initials: RM
authors.lastname: Conry
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000276:immunology* / Q000493:pharmacokinetics / Q000627:therapeutic use; D017252:CD3 Complex / Q000276:immunology*; D016207:Cytokines / Q000097:blood; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D007167:Immunotherapy; D008297:Male; D008545:Melanoma / Q000276:immunology* / Q000473:pathology / Q000628:therapy*; D008875:Middle Aged; D009362:Neoplasm Metastasis / Q000276:immunology / Q000628:therapy
chemical_list: D000911:Antibodies, Monoclonal; D017252:CD3 Complex; D016207:Cytokines