检索结果-南通市图书馆

Journal of Thermal Science 2022年第3期31卷 751-764页

作者： wu zhuang ZHU Huiren GAO Qiang LIU Cunliang LI Lin ZHANG Zheng School of Power and Energy Northwestern Polytechnical UniversityXi’an710071China Shaanxi Key Laboratory of Thermal Sciences in Aero-engine System Xi’an710071China

A combined experimental and numerical investigation of the heat transfer and flow characteristics of the roughened target plate has been conducted.All the data are compared with the flat plate.Three novel streamlined roughness elements are proposed:similar round protuberance,similar trapezoidal straight rib,and similar trapezoidal curved rib.The experiments are carried out in a perspex model using the transient thermochromic liquid crystal method.The effect of jet Reynolds number,rib height,and rib shape on the Nusselt number and flow discharge coefficient has been investigated.Higher ribs provide higher heat transfer enhancement.The curved ribs provide better heat transfer performance.Within the experimental scope,combined straight rib plate and combined curved rib plate increase the area averaged Nusselt number by 11.5%and 13.8%respectively.The experiment is complemented by a numerical part,which can provide flow field analysis and the Nusselt number on the surface of the small size roughness element.The numerical results show the protuberance can shorten the nozzle to plate distance and make the shifting point move forward.The ribs have a guidance effect on crossflow and reduce the transverse interference to the downstream jet.The transferred heat flux caused by the side surface of the roughness element is very obvious.The heat flux contributed by the side surface of the protuberance and ribs can reach 26%and 10%respectively.

关键词： impingement cooling roughness element heat transfer flow discharge coefficient

Numerical Investigation of Flow and Heat Transfer in Vane Impingement/Effusion Cooling with Various Rib/Dimple Structure

在线全文

学校读者我要写书评

暂无评论

Journal of Thermal Science 2023年第4期32卷 1357-1377页

作者： WANG Mingrui ZHU Huiren LIU Cunliang WANG Rui wu zhuang YAO Chunyi School of Power and Energy Northwestern Polytechnical UniversityXi’an710129China

By investigating heat transfer and flow structures of dimples,orthogonal ribs,and V-shaped ribs in the impingement/effusion cooling,the article is dedicated to selecting a best-performing internal cooling structure for a turbine vane.The overall cooling effectiveness and coolant consumption are adopted to evaluate the cooling performance.To analyze the influence of structural modification,the flow field is investigated on chordwise/spanwise sections and the target surface.The blockage effect on crossflow can protect jet flow,resulting in higher heat transfer performance of the target surface.Ribs own a stronger blockage effect than dimples.Compared with the blockage effect,the influence of the rib shape is negligible.By installing dimples between ribs,heat transfer is augmented further.The introduction of ribs/dimples leads to higher discharge coefficients of jet nozzles but lower discharge coefficients of film holes.Thus,the film cooling deteriorates.Meanwhile,the installation of the ribs and dimples decreases total coolant consumption.The effect of ribs/dimples on heat transfer and effusion condition of internal and external cooling is analyzed.The best-performing cooling structure is the target surface with dimples and orthogonal ribs,which decreases the wall temperature and coolant consumption by 14.57-28.03 K and 1.19%-1.81%respectively.This article concludes the flow mechanism for dimples and influence factors on the cooling performance,which may serve as guidance for the turbine vane design.

关键词： conjugate heat transfer impingement cooling dimple V-shape rib discharge coefficient

在线全文

学校读者我要写书评

暂无评论

大历史观视野下的中华民族现代文明

理论与改革 2024年第1期 14-30页

作者：李武装西安工程大学马克思主义学院

在“以文明求复兴”的新时代,中华民族现代文明无疑是中华文化的精髓和中华民族的最新精神标识,是新时代中国向世界表达自身形象的文化名片,是新一代中国共产党人治国理政的文化战略及其宣传思想主线,是中国式现代化的文化形态。其出场... 详细信息

在“以文明求复兴”的新时代,中华民族现代文明无疑是中华文化的精髓和中华民族的最新精神标识,是新时代中国向世界表达自身形象的文化名片,是新一代中国共产党人治国理政的文化战略及其宣传思想主线,是中国式现代化的文化形态。其出场不仅表征着拥有5000多年历史的中华文明蕴含的“文化生命体”因子和“历史主动精神”被全面激活,至关重要的是,透射出我们正努力将那个“古今中西之争”——实质是“中国向何处去”问题,转换为文化古今相通与文明交流互鉴以及以中国智慧并“焕新之力”促进文化“涵化”的志气、骨气、底气。立足习近平文化思想高度审视中华民族现代文明,应当优先基于大历史观探赜索隐其历史逻辑、理论逻辑和实践逻辑,这三者不仅构成中华民族现代文明之“大写的逻辑”谱系,而且包蕴并体现着习近平文化思想“明体达用、体用贯通”的理论品格和鲜明特质。无论是从历史逻辑还是理论逻辑出发,建设中华民族现代文明本质上不啻于在“两个结合”特别是“第二个结合”方法论基础上的新的政治文明史观的书写或塑造;着眼于实践逻辑,则应进一步拓展和落实其在政治表达、民族团结和文明互鉴等具体维面之实际因应功效。

关键词：习近平文化思想中华民族现代文明大历史观政治文明历史主动精神 “两个结合”

Efficacy,safety and pharmacokinetics of Unecritinib(TQ-B3101)for patients with ROS1 positive advanced non-small cell lung cancer:a Phase I/II Trial

在线全文

学校读者我要写书评

暂无评论

Signal Transduction and Targeted Therapy 2023年第7期8卷 3536-3546页

作者： Shun Lu Hongming Pan Lin wu Yu Yao Jianxing He Yan Wang Xiuwen Wang Yong Fang Zhen Zhou Xicheng Wang Xiuyu Cai Yan Yu Zhiyong Ma Xuhong Min Zhixiong Yang Lejie Cao Huaping Yang Yongqian Shu wu zhuang Shundong Cang Jian Fang Kai Li zhuang Yu Jiuwei Cui Yang Zhang Man Li Xinxuan Wen Jie Zhang Weidong Li Jianhua Shi Xingxiang Xu Diansheng Zhong Tao Wang Jiajia Zhu Department of Medical Oncology Shanghai Chest HospitalSchool of MedicineShanghai Jiao Tong University200030 ShanghaiChina Department of Medical Oncology Sir Run Run Shaw HospitalZhejiang University310016 HangzhouChina Department of Thoracic Medical Oncology The Affiliated Cancer Hospital of Xiangya School of MedicineCentral South University(Hunan Cancer Hospital)410031 ChangshaChina Department of Medical Oncology The First Affiliated Hospital of Xi’an Jiaotong University710061 XianChina Department of Thoracic Surgery The First Affiliated Hospital of Guangzhou Medical University510120 GuangzhouChina Department of Medical Oncology National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical College100021 BeijingChina Department of Oncology Qilu Hospital of Shandong University250012 JinanChina Department of Oncology The First Affiliated Hospital/School of Clinical Medicine of Guangdong Pharmaceutical University510699 GuangzhouChina Department of Medical Oncology Sun Yat-sen University Cancer Center510060 GuangzhouChina Department of Respiratory Medicine Harbin Medical University Cancer Hospital150081 HarbinChina Department of Medical Oncology Henan Tumor Hospital450003 ZhengzhouChina Department of Oncology Radiotherapy Anhui Chest Hospital230022 HefeiChina Department of Cancer Center Affiliated Hospital of Guangdong Medical University524000 ZhanjiangChina Department of Respiratory Medicine The First Affiliated Hospital of the University of Science and Technology of ChinaAnhui Provincial Hospital230031 HefeiChina Department of Respiratory and Critical Care Medicine Xiangya Hospital Central South University410008 ChangshaChina Department of Cancer Center Jiangsu Province Hospital210029 NanjingChina Department of Thoracic Oncology Fujian Cancer Hospital and Fujian Medical University Cancer Hospital350014 FuzhouChina Department of Medical Oncology Henan Province People’s Hospital450003 ZhengzhouCh

This phase I/II trial characterized the tolerability,safety,and antitumor activities of unecritinib,a novel derivative of crizotinib and a multi-tyrosine kinase inhibitor targeting ROS1,ALK,and c-MET,in advanced tumors and ROS1 inhibitor-naive advanced or metastatic non-small cell lung cancer(NSCLC)harboring ROS1 rearrangements.Eligible patients received unecritinib 100,200.

关键词： patients lung cancer

维普期刊数据库评论

在线全文

维普期刊数据库

学校读者我要写书评

暂无评论

齿轮精密塑性成形理论技术装备研究与应用

塑性工程学报 2024年第4期31卷 56-73页

作者：华林冯玮韩星会庄武豪武汉理工大学现代汽车零部件技术湖北省重点实验室湖北武汉430070 武汉理工大学材料复合新技术国家重点实验室湖北武汉430070 武汉理工大学材料科学与工程学院湖北武汉430070

齿轮是传动系统的核心基础件,被广泛应用于机械、汽车、航空航天装备等领域。齿轮传统制造技术为切削加工,其材料利用率低、加工周期长,特别是金属流线切断,损害齿轮性能,无法满足高端装备发展需求。齿轮精密塑性成形制造技术具有节能... 详细信息

齿轮是传动系统的核心基础件,被广泛应用于机械、汽车、航空航天装备等领域。齿轮传统制造技术为切削加工,其材料利用率低、加工周期长,特别是金属流线切断,损害齿轮性能,无法满足高端装备发展需求。齿轮精密塑性成形制造技术具有节能、节材、高效和优质等特点,是高性能齿轮技术发展方向。阐述了齿轮精密塑性成形理论方法,分析了国内外圆锥直齿轮、圆柱直齿轮和圆柱螺旋/斜齿轮精密成形技术特点;介绍了齿轮精密成形典型装备及产线,总结了齿轮无切削摆辗精密成形和锻造精密成形应用情况。此外,展示了圆锥螺旋齿轮多自由度包络成形和非圆齿轮锻造成形新方法,为高性能齿轮无切削成形制造技术装备研究与应用提供了参考。

关键词：齿轮精密塑性成形精密成形理论精密成形技术精密成形装备

Envonalkib versus crizotinib for treatment-naive ALK-positive non-small cell lung cancer: a randomized, multicenter, open-label, phase III trial

在线全文

学校读者我要写书评

暂无评论

Signal Transduction and Targeted Therapy 2023年第9期8卷 4338-4345页

作者： Yunpeng Yang Jie Min Nong Yang Qitao Yu Ying Cheng Yanqiu Zhao Manxiang Li Hong Chen Shou’an Ren Jianying Zhou wu zhuang Xintian Qin Lejie Cao Yan Yu Jian Zhang Jianxing He Jifeng Feng Hao Yu Li Zhang Wenfeng Fang Department of Medical Oncology Sun Yat-sen University Cancer CenterState Key Laboratory of Oncology in South ChinaCollaborative Innovation Center for Cancer MedicineGuangzhou 510060China Department of Oncology The Second Affiliated Hospital of Air Force Medical UniversityXi’an 710038China Department of Medical Oncology Lung Cancer and Gastrointestinal UnitHunan Cancer Hospital/The Affiliated Cancer Hospital of Xiangya School of MedicineCentral South UniversityChangsha 410013China Department of Medical Oncology of Respiratory Affiliated Tumor Hospital of Guangxi Medical UniversityGuangxiNanning 530021China Department of Thoracic Medical Oncology Jilin Provincial Cancer HospitalChangchun 130012China Department of Medical Oncology The Affiliated Cancer Hospital of Zhengzhou UniversityZhengzhou 450003China Department of Respiratory First Affiliated Hospital of Xian Jiaotong UniversityXi’an 710061China Department of Respiratory and Critical Care Medicine The First Affiliated Hospital of Chongqing Medical UniversityChongqing 400050China Department of Respiratory The First Hospital of Shanxi Medical UniversityTaiyuan 030001China Department of Respiratory Disease The First Affiliated HospitalZhejiang University School of MedicineHangzhou 310003China Department of Medical Oncology Fujian Cancer HospitalFuzhou 350014China The First Department of Oncology The First Affiliated Hospital of Guangdong Pharmaceutical UniversityGuangzhou 510699China Department of Respiratory and Critical Care Medicine Anhui Provincial HospitalHefei 230000China Department of Respiratory Medicine Affiliated Cancer Hospital of Harbin Medical UniversityHarbin 150000China Department of Respiratory Medicine The First Affiliated Hospital of Air Force Medical UniversityXi’an 710032China Department of Cardiothoracic Surgery The First Affiliated Hospital of Guangzhou Medical CollegeGuangzhou Research Institute of Respiratory Disease and China State Key Laboratory of Respiratory DiseaseGuangzhou 510120China Department

Anaplastic lymphoma kinase(ALK)rearrangements are present in about 5–6%of non-small cell lung cancer(NSCLC)cases and associated with increased risks of central nervous system(CNS)involvement.Envonalkib,a novel ALK inhibitor,demonstrated promising anti-tumor activity and safety in advanced ALK-positive NSCLC in the first-in-human phase I study.This phase III trial(ClinicalTrials.gov NCT04009317)investigated the efficacy and safety of first-line envonalkib in advanced ALK-positive NSCLC cases.Totally 264 participants were randomized 1:1 to receive envonalkib(n=131)or crizotinib(n=133).Median independent review committee(IRC)-assessed progression-free survival(PFS)times were 24.87(95%confidence interval[CI]:15.64–30.36)and 11.60(95%CI:8.28–13.73)months in the envonalkib and crizotinib groups,respectively(hazard ratio[HR]=0.47,95%CI:0.34–0.64,p<0.0001).IRC-assessed confirmed objective response rate(ORR)was higher(81.68%vs.70.68%,p=0.056)and duration of response was longer(median,25.79[95%CI,16.53–29.47]vs.11.14[95%CI,9.23–16.59]months,p=0.0003)in the envonalkib group compared with the crizotinib group.In participants with baseline brain target lesions,IRC-assessed CNS-ORR was improved with envonalkib compared with crizotinib(78.95%vs.23.81%).Overall survival(OS)data were immature,and median OS was not reached in either group(HR=0.84,95%CI:0.48–1.47,p=0.5741).The 12-month OS rates were 90.6%(95%CI,84.0%–94.5%)and 89.4%(95%CI,82.8%–93.6%)in the envonalkib and crizotinib groups,respectively.Grade≥3 treatment-related adverse events were observed in 55.73%and 42.86%of participants in the envonalkib and crizotinib groups,respectively.Envonalkib significantly improved PFS and delayed brain metastasis progression in advanced ALK-positive NSCLC.

关键词： crizotinib randomized cancer

Syndecan 4-c-ros oncogene 1 fusion as a mechanism of acquired resistance in epidermal growth factor receptor mutant lung adenocarcinoma

维普期刊数据库评论

在线全文

维普期刊数据库

学校读者我要写书评

暂无评论

Chinese Medical Journal 2019年第24期132卷 3015-3017页

作者： You-Cai Zhu Chun-Wei Xu Qu-Xia Zhang Wen-Xian Wang Lei Lei wu zhuang Department of Thoracic Disease Center Zhejiang Rongjun HospitalJiaxingZhejiang 314000China Department of Pathology Fujian Cancer HospitalFujian Medical University Cancer HospitalFuzhouFujian 350014China Department of Chemotherapy Zhejiang Cancer HospitalHangzhouZhejiang 310022China Department of Medical Thoracic Oncology Fujian Cancer HospitalFujian Medical University Cancer HospitalFuzhouFujian 350014China.

To the Editor:A 37-year-old Chinese woman,a nonsmoker,presented with adenocarcinoma of the left lung(stage IV)[Figure 1A],malignant pleural effusion,and multiple bone metastases in December 2014.Deoxyribonucleic acid sequencing of the tumor biopsy revealed an epidermal growth factor receptor(EGFR)exon 19 deletion,and treatment with gefitinib was consequently initiated in December 2014.There were no treatmentrelated side effects except for a grade 1 rash,and stable disease was achieved.Unfortunately,the patient did not experience long-term benefits and developed disease progression after only two months.A follow-up examination showed that extracranial disease and a small intracranial lesion had developed gradually.The patient then received whole-brain radiotherapy(30 Gy in ten fractions)and four cycles of single-agent pemetrexed in April 2015.Stable disease was achieved,which coincided with an improvement in the patient’s cough,shortness of breath,and general condition.The chemotherapy course was changed to two cycles of pemetrexed combined with cisplatin.A partial response(PR)was achieved,and the patient was treated with 14 cycles of pemetrexed alone as maintenance chemotherapy.The follow-up evaluations showed the patient’s condition to be stable;however,the patient’s disease progressed after 23 months.A computed tomography(CT)scan in March 2017 revealed that both the lung lesion and the malignant pleural effusion had increased in size[Figure 1B].The subsequent biopsy specimen was subjected to next-generation sequencing(NGS)and a Syndecan 4-c-ros oncogene 1(SDC4-ROS1)rearrangement was detected[Figure 1C].The patient then received crizotinib in April 2017,and a PR was achieved[Figure 1D].A CT scan done in August 2018 indicated the progression of the primary lesion in the left lung and malignant pleural effusion.However,the growth of the remaining lesions remained stable.

关键词： adenocarcinoma Figure smoke

Spectroscopic characterization and photochemistry of the Criegee intermediate CF_(3)C(H)OO

在线全文

学校读者我要写书评

暂无评论

Journal of Environmental Sciences 2022年第4期34卷 160-169页

作者： Lina Wang zhuang wu Bo Lu Xiaoqing Zeng Department of Chemistry Shanghai Key Laboratory of Molecular Catalysts and Innovative MaterialsFudan UniversityShanghai 200433China

Criegee intermediates(CIs),also known as carbonyl oxide,are reactive intermediates that play an important role in the atmospheric chemistry.Investigation on the structures and reactivity of CIs is of fundamental importance in understanding the underlying mechanism of their atmospheric reactions.In sharp contrast to the intensively studied parent molecule(CH_(2)OO)and the alkyl-substituted derivatives,the knowledge about the fluorinated analogue CF_(3)C(H)OO is scarce.By carefully heating the triplet carbene CF_(3)CH in an O2-doped Ar-matrix to 35 K,the elusive carbonyl oxide CF_(3)C(H)OO in syn-and anti-conformations has been generated and characterized with infrared(IR)and ultraviolet-visible(UV-vis)spectroscopy.The spectroscopic identification is supported by^(18)O-labeling experiments and quantum chemical calculations at the B3 LYP/6-311++G(3df,3pd)and MP2/6-311++G(2d,2p)levels.Upon the long-wavelength irradiation(λ>680 nm),both conformers of CF_(3)C(H)OO decompose to give trifluoroacetaldehyde CF_(3)C(H)O and simultaneously rearrange to the isomeric dioxirane,cyclic-CF_(3)CH(OO),which undergoes isomerization to the lowest-energy carboxylic acid CF_(3)C(O)OH upon UV-light excitation at 365 nm.The O_(2)-oxidation of CF_(3)CH via the intermediacy of CF_(3)C(H)OO and cyclic-CF_(3)CH(OO)might provide new insight into the mechanism for the degradation of hydro-chlorofluorocarbon CF_(3)CHCl_(2)(HCFC-123)in the atmosphere.

关键词： Criegee intermediates CF_(3)COOH(TFA) CF_(3)CHCl_(2)(HCFC-123) Photochemistry Matrix-isolation spectroscopy

Equivalent efficacy study of QL1101 and bevacizumab on untreated advanced non-squamous non-small cell lung cancer patients: a phase 3 randomized, double-blind clinical trial

在线全文

学校读者我要写书评

暂无评论

Cancer Biology & Medicine 2021年第3期18卷 816-824页

作者： Tianqing Chu Jun Lu Minghong Bi Helong Zhang wu zhuang Yan Yu Jianhua Shi Zhendong Chen Xiaochun Zhang Qisen Guo Quan Liu Huijuan wu Jian Fang Yi Hu Xiuwen Wang Cuicui Han Kai Li Baohui Han Department of Pulmonary Medicine Shanghai Chest HospitalShanghai Jiao Tong UniversitySha nghai 200030China Department of Oncology The First Affiliated Hospital of Bengbu Medical CollegeBengbu 233004China Department of Oncology Tangdu HospitalAir Force Medical University of PLAXi'an 710038China Department of Medical Thoracic Oncology Fujian Cancer HospitalFujian Medical University Cancer HospitalFuzhou 350014China Department of Oncology Harbin Medical University Cancer HospitalHarbin 150081China Department of Oncology Linyi Cancer HospitalLinyi 276000China Department of Oncology The Second Hospital of Anhui Medical UniversityHefei 230601China Department of Oncology The Affiliated Hospital of Qingdao UniversityQingdao 266071China Department of Internal Medicine Shandong Cancer Hospital Affiliated to Shandong UniversityJinan 250117China Department of Oncology Affiliated Hospital of Jiang Nan UniversityWuxi 214122China Department of Internal Medicine Henan Province Tumor HospitalZhengzhou UniversityZhengzhou 450008China Department of Thoracic OncologyⅡ Peking University Cancer Hospital and InstituteBeijing 100142China Department of Oncology Chinese PLA General HospitalBeijing 100039China Department of Oncology Qilu Hospital of Shandong UniversityJinan 250012China Department of Clinical Research Centre Qilu Pharmaceutical Co.LtdJinan 250101China Department of Thoracic Oncology Tianjin Medical University Cancer Institute and HospitalNational Clinical Research Center for CancerKey Laboratory of Cancer Prevention and TherapyTianjinTianjin’s Clinical Research Center for CancerTianjin 300060China

Objective:This phase 3 study aimed to test equivalence in efficacy and safety for QL1101,a bevacizumab analogue in Chinese patients with untreated locally advanced non-squamous non-small cell lung cancer(NSCLC).Methods:Eligible patients were randomly assigned 1:1 to receive carboplatin and paclitaxel in combination with either QL1101 or bevacizumab,15 mg/kg every 3-week for 6 cycles.This was followed by maintenance treatment with single agent QL1101 every 3-week.The primary end-point was objective response rate(ORR),with secondary end-points being progression-free survival(PFS),overall survival(OS),disease control rate(DCR),and adverse events(AEs).Results:Of 675 patients,535 eligible patients were randomized to the QL1101 group(n=269)and bevacizumab group(n=266).ORRs were 52.8%and 56.8%,respectively,for the QL1101 and bevacizumab groups,with an ORR hazard ratio 0.93(95%confidence interval:0.8-0131.1).The PFS,OS,DCR,and AEs were comparable between the 2 groups,which remained the same after stratification according to epidermal growth factor receptor mutation or smoking history.Conclusions:QL1101 showed similar efficacy and safety profiles as compared to bevacizumab among Chinese patients with untreated locally advanced non-squamous NSCLC.

关键词： Biosimilar bevacizumab equivalence non-squamous NSCLC clinical efficacy

Safety and activity of WX-0593(Iruplinalkib)in patients with ALK-or ROS1-rearranged advanced non-small cell lung cancer:a phase 1 dose-escalation and dose-expansion trial

在线全文

学校读者我要写书评

暂无评论

Signal Transduction and Targeted Therapy 2022年第2期7卷 573-582页

作者： Yuankai Shi Jian Fang Xuezhi Hao Shucai Zhang Yunpeng Liu Lin Wang Jianhua Chen Yi Hu Xiaosheng Hang Juan Li Chunling Liu Yiping Zhang Zhehai Wang Yanping Hu Kangsheng Gu Jian’an Huang Liangming Zhang Jinlu Shan Weiwei Ouyang Yanqiu Zhao wu zhuang Yan Yu Jun Zhao Helong Zhang Pei Lu Weidong Li Meimei Si Mingjing Ge Huaize Geng National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital Chinese Academy of Medical Sciences&Peking Union Medical CollegeBeijing Key Laboratory of Clinical Study on Anticancer Molecular Targeted Drugs100021 BeijingP.R.China Beijing Cancer Hospital 100142 BeijingP.R.China Beijing Chest Hospital Capital Medical University101149 BeijingP.R.China The First Hospital of China Medical University 110001 ShenyangP.R.China Hunan Cancer Hospital 410000 ChangshaP.R.China Chinese PLA General Hospital 100853 BeijingP.R.China Affiliated Hospital of Jiangnan University 214062 WuxiP.R.China Sichuan Cancer Hospital 610041 ChengduP.R.China Affiliated Tumour Hospital of Xinjiang Medical University 830000 UrumqiP.R.China Zhejiang Cancer Hospital 310022 HangzhouP.R.China Shandong Cancer Hospital and Institute Shandong First Medical University and Shandong Academy of Medical Sciences250117 JinanP.R.China Hubei Cancer Hospital 430079 WuhanP.R.China The First Affiliated Hospital of Anhui Medical University 230022 HefeiP.R.China The First Affiliated Hospital of Soochow University 215006 SuzhouP.R.China Yantai Yuhuagding Hospital Yantai 264000P.R.China Army Medical Center of People’s Liberation Army 400042 ChongqingP.R.China Guizhou Cancer Hospital 520100 GuiyangP.R.China Henan Cancer Hospital 450008 ZhengzhouP.R.China Fujian Province Cancer Hospital 350014 FuzhouP.R.China Harbin Medical University Cancer Hospital 150081 HarbinP.R.China Tangdu Hospital of the Fourth Military Medical University 710038 Xi’anP.R.China Liuzhou People’s Hospital 545006 LiuzhouP.R.China Cancer Center of Guangzhou Medical University 510095 GuangzhouP.R.China Qilu Pharmaceutical Co. Ltd250101 JinanP.R.China

WX-0593(Iruplinalkib)is a novel,highly selective oral ALK and ROS1 tyrosine kinase inhibitor(TKI).In this study,the safety,antitumor activity,and pharmacokinetics of WX-0593 were evaluated in advanced non-small cell lung cancer(NSCLC)patients with ALK or ROS1 rearrangement.In the dose-escalation phase and dose-expansion phase,patients were treated with WX-0593 until disease progression,unacceptable toxicity,or subject withdrawal.In the dose-escalation phase,the primary endpoints were maximum tolerated dose(MTD),dose-limiting toxicity(DLT),and safety assessed by investigators.In the dose-expansion phase,the primary endpoint was objective response rate(ORR)assessed by investigators.Between September 25,2017 and October 15,2018,a total of 153 patients received WX-0593 treatment.Two dose-limiting toxicities(DLTs)including one grade 3 QT interval prolonged and one grade 2 chronic heart failure were reported at the dose of 300 mg in one patient.MTD was not reached.Overall,140 of the 152(92%)patients experienced treatment-related adverse events(TRAEs)and 35 of the 152(23%)patients had TRAEs≥grade 3.The overall ORR was 59.3%(32 of 54)for the dose-escalation phase and 56.6%(56 of 99)for the dose-expansion phase.For patients who were ALK-rearranged and ALK TKI naive,the ORR were 81.0%(17 of 21)in the dose-escalation phase and 76.3%(29 of 38)in the dose-expansion phase,and for patients who previously received crizotinib as the only ALK TKI,the ORR were 38.1%(8 of 21)and 45.7%(21 of 46)for the two phases,respectively.For patients who were ROS1-rearranged,the ORR were 30.0%(3 of 10)in the dose-escalation phase and 44.4%(4 of 9)in the dose-expansion phase.WX-0593 showed favorable safety and promising antitumor activity in advanced NSCLC patients with ALK or ROS1 rearrangement.

关键词： patients expansion phase