Specific Targeting, Biodistribution, and Lack of Immunogenicity of Chimeric Anti-GD3 Monoclonal Antibody KM871 in Patients With Metastatic Melanoma: Results of a Phase I Trial Academic Article uri icon

abstract

  • KM871 is a chimeric monoclonal antibody against the ganglioside antigen GD3, which is highly expressed on melanoma cells. We conducted an open-label, dose escalation phase I trial of KM871 in patients with metastatic melanoma.Seventeen patients were entered onto one of five dose levels (1, 5, 10, 20, and 40 mg/m2). Patients received three infusions of KM871 at 2-week intervals, with the first infusion of KM871 trace-labeled with indium-111 (111In) to enable assessment of biodistribution in vivo. Biopsies of metastatic melanoma sites were performed on days 7 to 10.Fifteen of 17 patients completed a cycle of three infusions of KM871. No dose-limiting toxicity was observed during the trial; the maximum-tolerated dose was therefore not reached. Three patients (at the 1-, 5-, and 40-mg/m2 dose levels) developed pain and/or erythema at tumor sites consistent with an inflammatory response. No normal tissue uptake of 111In-KM871 was observed, and tumor uptake of 111In-KM871 was observed in all lesions greater than 1.5 cm (tumor biopsy 111KM871 uptake results: range, 0.001% to 0.026% injected dose/g). The ratio of maximum tumor to normal tissue was 15:1. Pharmacokinetic analysis revealed a 111In-KM871 terminal half-life of 7.68 +/- 2.94 days. One patient had a clinical partial response that lasted 11 months. There was no serologic evidence of human antichimeric antibody in any patient, including one patient who received 16 infusions over a 12-month period.This study is the first to demonstrate the biodistribution and specific targeting of an anti-GD3 antibody to metastatic melanoma in patients. The long half-life and lack of immunogenicity of KM871 makes this antibody an attractive potential therapy for patients with metastatic melanoma.

authors

  • Scott, Andrew M
  • Lee, Fook-Thean
  • Hopkins, Wendie
  • Cebon, Jonathan S
  • Wheatley, Jennifer M
  • Liu, Zhanqi
  • Smyth, Fiona E
  • Murone, Carmel
  • Sturrock, Susan
  • MacGregor, Duncan
  • Hanai, Nobuo
  • Inoue, Kengo
  • Yamasaki, Motoo
  • Brechbiel, Martin W
  • Davis, Ian D
  • Murphy, Roger
  • Hannah, Anthony
  • Lim-Joon, Michael
  • Chan, Tony
  • Chong, Geoffrey
  • Ritter, Gerd
  • Hoffman, Eric W
  • Burgess, Antony W
  • Old, Lloyd J

publication date

  • October 2001