https://scholars.lib.ntu.edu.tw/handle/123456789/629465
標題: | Evaluation of combination treatment with DS-1205c, an AXL kinase inhibitor, and osimertinib in metastatic or unresectable EGFR-mutant non-small cell lung cancer: results from a multicenter, open-label phase 1 study | 作者: | CHIH-HSIN YANG Su, Wu-Chou Chiu, Chao-Hua Shiah, Her-Shyong Lee, Kang-Yun Hsia, Te-Chun Uno, Makiko Crawford, Nigel Terakawa, Hiroshi Chen, Wen-Chi Takayama, Gensuke Hsu, Ching Hong, Ying Saintilien, Carline McGill, Joseph Chang, Gee-Chen |
關鍵字: | AXL kinase inhibitor; Advanced non-small cell lung cancer; DS-1205c; Epidermal growth factor receptor; Inoperable non-small cell lung cancer; Oncology | 公開日期: | 9-三月-2023 | 來源出版物: | Investigational new drugs | 摘要: | The objective of this study was to evaluate the safety and tolerability of DS-1205c, an oral AXL-receptor inhibitor, in combination with osimertinib in metastatic or unresectable EFGR-mutant non-small cell lung cancer (NSCLC) patients who developed disease progression during EGFR tyrosine kinase inhibitor (TKI) treatment. An open-label, non-randomized phase 1 study was conducted in Taiwan, in which 13 patients received DS-1205c monotherapy at a dosage of 200, 400, 800, or 1200 mg twice daily for 7 days, followed by combination treatment with DS-1205c (same doses) plus osimertinib 80 mg once daily in 21-day cycles. Treatment continued until disease progression or other discontinuation criteria were met. At least one treatment-emergent adverse event (TEAE) was reported in all 13 patients treated with DS-1205c plus osimertinib; with ≥ 1 grade 3 TEAE in 6 patients (one of whom also had a grade 4 increased lipase level), and 6 patients having ≥ 1 serious TEAE. Eight patients experienced ≥ 1 treatment-related AE (TRAE). The most common (2 cases each) were anemia, diarrhea, fatigue, increased AST, increased ALT, increased blood creatinine phosphokinase, and increased lipase. All TRAEs were non-serious, with the exception of an overdose of osimertinib in 1 patient. No deaths were reported. Two-thirds of patients achieved stable disease (one-third for > 100 days), but none achieved a complete or partial response. No association between AXL positivity in tumor tissue and clinical efficacy was observed. DS-1205c was well-tolerated with no new safety signals in patients with advanced EGFR-mutant NSCLC when administered in combination with the EFGR TKI osimertinib. ClinicalTrials.gov ; NCT03255083. |
URI: | https://scholars.lib.ntu.edu.tw/handle/123456789/629465 | ISSN: | 01676997 | DOI: | 10.1007/s10637-023-01341-y |
顯示於: | 腫瘤醫學研究所 |
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