高级检索
当前位置: 首页 > 详情页

Phase Ia/Ib Study of the Selective MET Inhibitor, Savolitinib, in Patients with Advanced Solid Tumors: \nSafety, Efficacy, and Biomarkers

文献详情

资源类型:
WOS体系:
Pubmed体系:

收录情况: ◇ SCIE

机构: [1]Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Early Drug Development Center, Peking University Cancer Hospital & Institute, Beijing, People’s Republic of China [2]Department of Medical Oncology, Zhongshan Hospital, and Center of Evidence-Based Medicine, Fudan University, Shanghai, People’s Republic of China [3]Department of Respiratory Medicine, Harbin Medical University Cancer Hospital, Harbin, People’s Republic of China [4]Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Gastrointestinal Oncology/Early Drug Development Center, Peking University Cancer Hospital & Institute, Beijing, People’s Republic of China [5]Gastrointestinal Oncology, Harbin Medical University Cancer Hospital, Harbin, People’s Republic of China [6]Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of China [7]Department of Medical Oncology, The First Affiliated Hospital of Zhejiang University, Hangzhou, People’s Republic of China [8]Department of Gastrointestinal Oncology, The Fifth Medical Center, Chinese PLA General Hospital, Beijing, People’s Republic of China [9]Department of Thoracic Surgery/Oncology, First Affiliated Hospital of Guangzhou Medical University, Guangzhou, People’s Republic of China [10]State Key Laboratory and National Clinical Research Center for Respiratory Disease, Guangzhou, People’s Republic of China [11]Department of Medical Oncology, The First Hospital of China Medical University, Shenyang, People’s Republic of China [12]State Key Laboratory of Oncology in South China, Guangzhou, People’s Republic of China [13]Collaborative Innovation Center for Cancer Medicine, Guangzhou, People’s Republic of China [14]Department of Medical Oncology, Sun Yat-sen University Cancer Center, Guangzhou, People’s Republic of China [15]Department of Medical Oncology, the Fourth Hospital of Hebei Medical University, Shijiazhuang, People’s Republic of China [16]Department of Respiratory and Critical Care Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People’s Republic of China [17]Department of Medical Oncology, Fudan University Shanghai Cancer Center, Shanghai, People’s Republic of China [18]Cancer Hospital Chinese Academy of Medical Sciences, Shenzhen Center, Shenzhen, People’s Republic of China [19]Cancer Center, The First Hospital of Jilin University, Changchun, Jilin, People’s Republic of China [20]Department of Medical Oncology, Chinese Academy of Medical Science, Peking Union Medical College Hospital, Beijing, People’s Republic of China [21]Hutchison China MediTech Limited, Shanghai, People’s Republic of China [22]The Comprehensive Cancer Centre of Drum Tower Hospital, Medical School of Nanjing University & Clinical Cancer Institute of Nanjing University, Nanjing, People’s Republic of China
出处:
ISSN:

关键词: savolitinib C-met inhibitor targeted therapy biomarker

摘要:
Background Savolitinib has shown good tolerability and preliminary efficacy, but efficacy biomarkers require investigation. The main purpose of this study was to confirm in Chinese patients the recommended phase II dose (RP2D) of savolitinib and to explore overall benefit in tumors bearing c-Met aberration. Methods This was an open-label, multi-center, 2-part phase I study. A starting dose of 600 mg QD was initiated in the escalation phase, utilizing a 3+3 design with repeated QD and BID dosing. In the dose expansion phase, we enrolled patients with gastric cancer and non-small cell lung cancer (NSCLC) with documented c-met aberration into 5 cohorts to further explore biomarkers. c-Met overexpression and amplification were assessed by immunohistochemistry and FISH, respectively. Results The safety analysis set included 85 patients. Only one dose-limiting toxicity (grade 3 fatigue) was reported in the 600 mg BID dosing group. The most frequent treatment-related adverse events were nausea (29.4%), vomiting (27.1%), and peripheral edema (21.2%). Notably, in gastric cancer, response was only observed in patients with MET amplification (copy number 9.7-18.4), with an objective response rate of 35.7% and a disease control rate of 64.3%. For patients with NSCLC bearing a MET exon 14 skipping mutation, obvious target lesion shrinkage was observed in 2 of 4 patients, although PR was not achieved. Conclusion The RP2D of savolitinib was established as 600 mg QD or 500 mg BID in Chinese patients. The promising response observed in patients with gastric cancer with c-met amplification and NSCLC with MET exon 14 skipping mutation warrants further investigation. ClinicalTrials.gov Identifier NCT0198555

基金:
语种:
被引次数:
WOS:
PubmedID:
中科院分区:
出版当年[2022]版:
大类 | 2 区 医学
小类 | 2 区 肿瘤学
最新[2025]版:
大类 | 2 区 医学
小类 | 2 区 肿瘤学
JCR分区:
出版当年[2022]版:
Q1 ONCOLOGY
最新[2024]版:
Q2 ONCOLOGY

影响因子: 最新[2024版] 最新五年平均 出版当年[2022版] 出版当年五年平均 出版前一年[2021版] 出版后一年[2023版]

第一作者:
第一作者机构: [1]Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Early Drug Development Center, Peking University Cancer Hospital & Institute, Beijing, People’s Republic of China
共同第一作者:
通讯作者:
通讯机构: [4]Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Gastrointestinal Oncology/Early Drug Development Center, Peking University Cancer Hospital & Institute, Beijing, People’s Republic of China [22]The Comprehensive Cancer Centre of Drum Tower Hospital, Medical School of Nanjing University & Clinical Cancer Institute of Nanjing University, Nanjing, People’s Republic of China [*1]Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Gastrointestinal Oncology/Early Drug Development Center, Peking University Cancer Hospital & Institute, Fu-Cheng Road 52, Hai-Dian District, Beijing 100142, People’s Republic of China. [*2]The Comprehensive Cancer Centre of Drum Tower Hospital, Medical School of Nanjing University & Clinical Cancer Institute of Nanjing University. No. 321, Zhongshan Road, Nanjing, 210000, People’s Republic of China.
推荐引用方式(GB/T 7714):
APA:
MLA:

资源点击量:42313 今日访问量:0 总访问量:1365 更新日期:2025-08-01 建议使用谷歌、火狐浏览器 常见问题

技术支持:重庆聚合科技有限公司 地址:河北省石家庄市健康路12号