Please use this identifier to cite or link to this item: http://ahro.austin.org.au/austinjspui/handle/1/9344
Title: 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.
Authors: Scott, Andrew M;Lee, Fook-Thean;Hopkins, Wendie;Cebon, Jonathan S;Wheatley, J M;Liu, Z;Smyth, Fiona E;Murone, Carmel;Sturrock, S;MacGregor, Duncan;Hanai, N;Inoue, K;Yamasaki, M;Brechbiel, Martin W;Davis, Ian D;Murphy, R;Hannah, A;Lim-Joon, M;Chan, T;Chong, Geoffrey;Ritter, G;Hoffman, E W;Burgess, Antony W;Old, Lloyd J
Affiliation: Ludwig Institute for Cancer Research, Melbourne Tumour Biology Branch, and Department of Nuclear Medicine and Centre for Positron Emission Tomography, Surgery, and Anatomical Pathology, Melbourne, Australia. ams@austin.unimelb.edu.au
Issue Date: 1-Oct-2001
Citation: Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology; 19(19): 3976-87
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.
Internal ID Number: 11579119
URI: http://ahro.austin.org.au/austinjspui/handle/1/9344
URL: http://www.ncbi.nlm.nih.gov/pubmed/11579119
Type: Journal Article
Subjects: Adult
Aged
Antibodies, Monoclonal.adverse effects.immunology.pharmacokinetics.therapeutic use
Antibody Specificity
Antigens, CD3.immunology
Biopsy
Female
Humans
Immunoconjugates.adverse effects.immunology.pharmacokinetics
Indium Radioisotopes.diagnostic use
Male
Melanoma.immunology.metabolism.radionuclide imaging.therapy
Middle Aged
Recombinant Fusion Proteins.adverse effects.immunology.pharmacokinetics.therapeutic use
Tissue Distribution
Appears in Collections:Journal articles

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