https://scholars.lib.ntu.edu.tw/handle/123456789/494897
標題: | Phase I Study of the Focal Adhesion Kinase Inhibitor BI 853520 in Japanese and Taiwanese Patients with Advanced or Metastatic Solid Tumors | 作者: | Doi T. CHIH-HSIN YANG Shitara K. Naito Y. ANN-LII CHENG Sarashina A. Pronk L.C. Takeuchi Y. CHIA-CHI LIN |
公開日期: | 2019 | 出版社: | Springer-Verlag France | 卷: | 14 | 期: | 1 | 起(迄)頁: | 57-65 | 來源出版物: | Targeted Oncology | 摘要: | Background: Focal adhesion kinase (FAK) inhibitors have demonstrated anti-tumor activity preclinically and are currently being evaluated in humans. A first-in-human study evaluating the novel FAK inhibitor BI?853520 in a predominantly Caucasian population with advanced or metastatic non-hematologic malignancies demonstrated acceptable tolerability and favorable pharmacokinetics. Objective: This study was undertaken to investigate the safety, tolerability, and maximum tolerated dose (MTD) of BI?853520 in Japanese and Taiwanese patients with advanced solid tumors. Patients and Methods: In this open-label, phase?I, dose-finding study, BI?853520 was administered once daily (QD) in a continuous daily dosing regimen with 28-day cycles and escalating doses to sequential cohorts of patients. Twenty-one patients (62% male; median age 65?years) were treated at two sites in Japan and Taiwan. Results: The median duration of treatment was 1.2?months (range 0.2–7.7). As no dose-limiting toxicities were observed during cycle 1 in the 50, 100, or 200?mg cohorts, the MTD of BI?853520 was determined to be 200?mg QD. Drug-related adverse events were reported in 19 patients (90%), and all except one were of grade?1 or 2. Pharmacokinetic parameters were supportive of a once-daily dosing schedule. A confirmed objective response rate of 5% and disease control rate of 29% were achieved; median duration of disease control was 3.7?months. Conclusions: This trial demonstrated a manageable and acceptable safety profile, favorable pharmacokinetics, and potential anti-tumor activity of BI?853520 in pretreated Japanese and Taiwanese patients with advanced or metastatic solid tumors. Clinical trials registration: NCT01905111. ? 2019, The Author(s). |
URI: | https://www.scopus.com/inward/record.uri?eid=2-s2.0-85061193461&doi=10.1007%2fs11523-019-00620-0&partnerID=40&md5=e236368c19f8ffeff9e6017a43243d3e https://scholars.lib.ntu.edu.tw/handle/123456789/494897 |
ISSN: | 1776-2596 | DOI: | 10.1007/s11523-019-00620-0 | SDG/關鍵字: | aspartate aminotransferase; bi 853520; bilirubin; creatinine; focal adhesion kinase inhibitor; unclassified drug; focal adhesion kinase 1; protein kinase inhibitor; PTK2 protein, human; abdominal pain; advanced cancer; aged; anemia; antineoplastic activity; area under the curve; Article; backache; cohort analysis; decreased appetite; dehydration; diarrhea; disease control; disease severity; dose response; drug accumulation; drug dose comparison; drug dose escalation; drug efficacy; drug half life; drug safety; drug tolerability; Dupuytren contracture; erectile dysfunction; fatigue; female; human; inguinal hernia; Japan; Japanese (people); maculopapular rash; major clinical study; male; maximum concentration; maximum tolerated dose; metastasis; multiple cycle treatment; nausea; open study; phase 1 clinical trial; priority journal; proteinuria; side effect; Taiwan; Taiwanese; treatment duration; vomiting; adult; clinical trial; follow up; metastasis; middle aged; neoplasm; pathology; prognosis; tissue distribution; Adult; Aged; Female; Focal Adhesion Kinase 1; Follow-Up Studies; Humans; Japan; Male; Maximum Tolerated Dose; Middle Aged; Neoplasm Metastasis; Neoplasms; Prognosis; Protein Kinase Inhibitors; Taiwan; Tissue Distribution |
顯示於: | 腫瘤醫學研究所 |
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