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

A. M. Scott, F. T. Lee, W. Hopkins, J. S. Cebon, J. M. Wheatley, Z. Liu, F. E. Smyth, C. Murone, S. Sturrock, D. MacGregor, N. Hanai, K. Inoue, M. Yamasaki, M. W. Brechbiel, I. D. Davis, R. Murphy, A. Hannah, M. Lim-Joon, T. Chan, G. ChongG. Ritter, E. W. Hoffman, A. W. Burgess, L. J. Old

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Abstract

Purpose: 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. Patients and Methods: 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. Results: 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. Conclusion: 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.

Original languageEnglish
Pages (from-to)3976-3987
Number of pages12
JournalJournal of Clinical Oncology
Volume19
Issue number19
DOIs
Publication statusPublished - 1 Oct 2001

Cite this

Scott, A. M., Lee, F. T., Hopkins, W., Cebon, J. S., Wheatley, J. M., Liu, Z., Smyth, F. E., Murone, C., Sturrock, S., MacGregor, D., Hanai, N., Inoue, K., Yamasaki, M., Brechbiel, M. W., Davis, I. D., Murphy, R., Hannah, A., Lim-Joon, M., Chan, T., ... Old, L. J. (2001). 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. Journal of Clinical Oncology, 19(19), 3976-3987. https://doi.org/10.1200/JCO.2001.19.19.3976