458PPHASE I STUDY OF ONTUXIZUMAB, A HUMANIZED MONOCLONAL ANTIBODY RECOGNIZING ENDOSIALIN/TUMOR ENDOTHELIAL MARKER1 (TEM1), IN JAPANESE PATIENTS WITH SOLID TUMOR

摘要: ABSTRACT Aim: Endosialin is a cell surface glycoprotein that expressed on cells involved in the development of tumor vasculature, primarily pericytes and stromal fibroblasts. Ontuxizumab humanized immunoglobulin G-1-kappa (IgG1/k) monoclonal antibody first clinical-stage agent to target endosialin. The has shown antitumor activity variety models its pharmacologic have distinct non-disease activities as compared other anti-vascular therapies, such no observed impact wound healing. Methods: Patients (pts) with solid who appropriate treatment were eligible study. Each cycle consisted four weeks. was administered weekly until disease progression or occurrence DLT 4 cohorts at 2, 4, 8 12 mg/kg schedule stepwise dose escalation manner. Results: Fifteen pts enrolled including three gastric cancer, two gastrointestinal tumor, breast cancer patient lung malignant pheochromocytoma, adrenocortical hypopharyngeal extraskeletal chondrosarcoma, thymic carcinoma, renal pelvis intrahepatic cholangiocarcinoma. No observed. Treatment related adverse events 5 15 most common grade 1 constipation (two pts), 2 hyperkalaemia infusion reaction pts). Cmax AUC values ontuxizumab after single administration increased dose-related Mean t1/2 85.2 - 219 hours multiple administrations. Human anti-human not detected. Of eight stable disease, one pt GIST failure imatinib sunitinib showed shrinkage by CT evaluation based Choi's criteria 12 mg/kg. longest duration 32 weeks for 4 mg/kg. Conclusions: well tolerated advanced tumors up currently being investigated Ph2 studies potential melanoma, metastatic colorectal carcinoma soft tissue sarcoma. Disclosure: T. Doi: Other substantive relationships:Participant Eisai sponsored speaker's bureau; Y. Naito: speaker‘s M. Tahara: Advisory Board: Eisai; K. Nakai: Employee Eisai. Own stock Eisai, A. Ohtsu: All authors declared conflicts interest.