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dc.contributor.authorScott, Andrew Men
dc.contributor.authorLee, Fook-Theanen
dc.contributor.authorHopkins, Wendieen
dc.contributor.authorCebon, Jonathan Sen
dc.contributor.authorWheatley, J Men
dc.contributor.authorLiu, Zen
dc.contributor.authorSmyth, Fiona Een
dc.contributor.authorMurone, Carmelen
dc.contributor.authorSturrock, Sen
dc.contributor.authorMacGregor, Duncanen
dc.contributor.authorHanai, Nen
dc.contributor.authorInoue, Ken
dc.contributor.authorYamasaki, Men
dc.contributor.authorBrechbiel, Martin Wen
dc.contributor.authorDavis, Ian Den
dc.contributor.authorMurphy, Ren
dc.contributor.authorHannah, Aen
dc.contributor.authorLim-Joon, Men
dc.contributor.authorChan, Ten
dc.contributor.authorChong, Geoffreyen
dc.contributor.authorRitter, Gen
dc.contributor.authorHoffman, E Wen
dc.contributor.authorBurgess, Antony Wen
dc.contributor.authorOld, Lloyd Jen
dc.identifier.citationJournal of Clinical Oncology; 19(19): 3976-87en
dc.description.abstractKM871 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.en
dc.subject.otherAntibodies, Monoclonal.adverse effects.immunology.pharmacokinetics.therapeutic useen
dc.subject.otherAntibody Specificityen
dc.subject.otherAntigens, CD3.immunologyen
dc.subject.otherImmunoconjugates.adverse effects.immunology.pharmacokineticsen
dc.subject.otherIndium Radioisotopes.diagnostic useen
dc.subject.otherMelanoma.immunology.metabolism.radionuclide imaging.therapyen
dc.subject.otherMiddle Ageden
dc.subject.otherRecombinant Fusion Proteins.adverse effects.immunology.pharmacokinetics.therapeutic useen
dc.subject.otherTissue Distributionen
dc.titleSpecific targeting, biodistribution, and lack of immunogenicity of chimeric anti-GD3 monoclonal antibody KM871 in patients with metastatic melanoma: results of a phase I trial.en
dc.typeJournal Articleen
dc.identifier.journaltitleJournal of Clinical Oncologyen
dc.identifier.affiliationLudwig Institute for Cancer Research, Melbourne Tumour Biology Branch, and Department of Nuclear Medicine and Centre for Positron Emission Tomography, Surgery, and Anatomical Pathology, Melbourne, Australiaen
dc.type.austinJournal Articleen
item.fulltextNo Fulltext-
item.openairetypeJournal Article-
item.cerifentitytypePublications- Imaging and Therapy- Newton-John Cancer Research Institute- Newton-John Cancer Research Institute- Newton-John Cancer Research Institute- Newton-John Cancer Wellness and Research Centre-
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