上海注射用MK-1022II期临床试验-HER3-DXd治疗胃肠道（GI）肿瘤的I/II期篮式研究

登记号	CTR20244798	试验状态	进行中
申请人联系人	张建芳	首次公示信息日期	2024-12-18
申请人名称	Merck Sharp & Dohme LLC/ 默沙东研发（中国）有限公司/ BSP Pharmaceuticals S.p.A

登记号	CTR20244798
相关登记号	暂无
药物名称	注射用MK-1022
药物类型	生物制品
临床申请受理号	企业选择不公示
适应症	胃肠道肿瘤
试验专业题目	一项评价Patritumab Deruxtecan治疗胃肠道肿瘤的安全性和有效性的I/II期研究
试验通俗题目	HER3-DXd治疗胃肠道（GI）肿瘤的I/II期篮式研究
试验方案编号	MK-1022-011	方案最新版本号	00
版本日期:	2024-06-06	方案是否为联合用药	否

申请人名称	[["Merck Sharp & Dohme LLC"],["默沙东研发（中国）有限公司"],["BSP Pharmaceuticals S.p.A"]]
联系人姓名	张建芳	联系人座机	010-58609021	联系人手机号	18611697663
联系人Email	nina_zhang@merck.com	联系人邮政地址	北京市-北京市-朝阳区中关村科技园电子城西区望京研发创新基地容达路21号楼1	联系人邮编	100012

评价Patritumab Deruxtecan治疗胃肠道肿瘤的安全性和有效性

试验分类	安全性和有效性	试验分期	II期	设计类型	平行分组
随机化	非随机化	盲法	开放	试验范围	国际多中心试验

年龄	18岁(最小年龄)至 无上限 (最大年龄)
性别	男+女
健康受试者	无
入选标准	[["2L结直肠癌：患有组织学确诊的、不可切除或转移性（美国癌症联合委员会第八版定义的IV期）结直肠腺癌。"],["2L结直肠癌：具有经当地确认的pMMR或非MSI-H肿瘤状态。"],["须仅接受过一线治疗，包括氟嘧啶类+奥沙利铂联合或不联合抗VEGF mAb或抗 EGFR mAb治疗，依据临床指征而定。"],["2L+胆道癌：组织学确诊为晚期（转移性）和/或不可切除的（局部晚期）BTC（肝内或肝外CCA或GBC）。"],["2L+胆管癌：对于不可切除或转移性疾病，既往应接受过1线以吉西他滨为基础的系统性治疗，或者已经接受过2线的系统性治疗（包括以吉西他滨为基础的治疗和非细胞毒性治疗[如分子靶向治疗或免疫治疗]）。"],["2L肝细胞癌：患有经组织学确诊的HCC（纤维板层和混合型肝细胞/胆管癌亚型不符合入选标准）。"],["2L肝细胞癌：须只接受过1线系统性免疫治疗，使用抗PD-1/PD-L1mAb单药或与其他检查点抑制剂或其他治疗联合使用。"],["性别不限，且提供知情同意时，年龄至少为18岁。"],["如果受试者可以产生精子，同意在干预期间和至少在末次研究干预后消除研究干预所需的时间内遵守相应的要求。"],["出生时性别指定为女性的受试者如果未处于妊娠期或哺乳期，且不是有生育能力的女性；或有生育能力则在研究期间以及研究干预末次给药后消除研究干预所需的时间内遵守相应的避孕要。"],["受试者已提供本研究的书面知情同意书。"],["存在由当地研究中心依据RECIST 1.1评估的可测量病灶并经BICR确认。"],["已提供存档肿瘤组织样本，并且已提供既往未接受过放疗的肿瘤病灶的治疗前粗针/切除活检样本。"],["因既往抗肿瘤治疗而发生AE的受试者必须已恢复至≤1级或基线水平。"],["有HIV感染的受试者必须在ART治疗后HIV得到良好控制。"],["预期寿命至少3个月。"],["HBsAg阳性的受试者如果在入组前接受HBV抗病毒治疗至少4周且HBV病毒载量不可检出，则有资格参加研究。"],["有HCV感染史的受试者如果筛选时检测不到HCV病毒载量，则有资格参加研究。"],["研究干预首次给药前28天内的ECOG PS为0或1分。"],["具有充分的器官功能。"]]
排除标准	[["有需要类固醇治疗的（非感染性）ILD/肺部炎症史，当前患有或筛选时无法通过影像学检查排除疑似ILD/肺部炎症。"],["并发肺部疾病导致的临床重度呼吸功能受损（基于研究者评估）。"],["患有具有临床意义的角膜疾病。"],["在研究干预给药前6个月内患有未控制的重大心血管疾病或脑血管疾病。"],["有卡波西肉瘤和/或多中心型Castleman病病史的HIV感染受试者。"],["仅HCC（队列3）受试者：合并有不能接受任何造影增强成像检查（CT或MRI）的医学禁忌症。"],["既往接受过拓扑异构酶I抑制剂（如伊立替康）或抗HER3抗体治疗和/或含拓扑异构酶I抑制剂exatecan衍生物（如德曲妥珠单抗）的ADC治疗。"],["C1D1前抗肿瘤治疗洗脱不充分。"],["C1D1前正在接受＞10 mg泼尼松或等效抗炎活性的长期全身皮质类固醇治疗或任何形式的免疫抑制治疗。"],["在研究干预首次给药前30天内接种过活疫苗或减毒活疫苗。"],["已知患有正在发生进展或过去3年内需要积极治疗的其他恶性肿瘤。"],["已知有活动性的CNS转移和/或癌性脑膜炎。"],["患有需要系统性治疗的活动性感染。"],["同时合并活动性乙型肝炎病毒感染和丙型肝炎病毒感染。"],["治疗研究者认为，既往或当前存在任何导致参与研究不符合受试者的最佳利益的情况。"],["已知对制剂中的原料药或非活性成分具有超敏反应。"],["受试者尚未从大手术中充分恢复或有持续的手术并发症。"],["无行为能力的受试者不具备参与资格。"]]

试验药	[["中文通用名:注射用MK-1022 英文通用名:MK-1022forinjection 商品名称:暂无","剂型:注射剂 规格:100mg/瓶 用法用量:2L结直肠癌：5.6mg/kg；2L+胆道癌：5.6mg/kg；2L肝细胞癌：采用BOIN设计探索两个预先指定的HER3-DXd剂量水平，4.8mg/kg（起始剂量）或5.6mg/kg。 用药时程:每三周用药一次，静脉注射，无最长暴露持续时间，治疗将持续至符合任何停药标准。"]] 序号 名称 用法
对照药	暂未填写此信息 序号 名称 用法

主要终点指标及评价时间	[["DLT（仅适用于队列3的剂量递增阶段）","方案规定的分析时间","安全性指标"],["AE","方案规定的分析时间","安全性指标"],["因AE终止研究干预","方案规定的分析时间","安全性指标"],["客观缓解：CR或PR","方案规定的分析时间","有效性指标"]] 序号 指标 评价时间 终点指标选择
次要终点指标及评价时间	[["DOR：对于经确认CR或PR的受试者，DOR定义为从首次记录到CR或PR证据直至疾病进展或任何原因导致死亡的时间，以先发生者为准","方案规定的分析时间","有效性指标"],["PFS：从研究干预第一天至首次记录到疾病进展或任何原因导致死亡的时间，以先发生者为准","方案规定的分析时间","有效性指标"],["OS：从研究干预第一天至任何原因导致死亡的时间","方案规定的分析时间","有效性指标"],["PK参数","方案规定的分析时间","有效性指标+安全性指标"]] 序号 指标 评价时间 终点指标选择

1	姓名	周俭	学位	医学博士	职称	院长，教授
	电话	021-64041990	Email	zhou.jian@zs-hospital.sh.cn	邮政地址	上海市-上海市-徐汇区枫林路180号
	邮编	200032	单位名称	复旦大学附属中山医院

[["复旦大学附属中山医院","周俭","中国","上海市","上海市"],["浙江大学医学院附属邵逸夫医院","潘宏铭","中国","浙江省","杭州市"],["河南省肿瘤医院","王居峰","中国","河南省","郑州市"],["中山大学附属第一医院","匡铭","中国","广东省","广州市"],["安徽医科大学第一附属医院","杜瀛瀛","中国","安徽省","合肥市"],["哈尔滨医科大学附属肿瘤医院","张艳桥","中国","黑龙江省","哈尔滨市"],["福建省肿瘤医院","陈奕贵","中国","福建省","福州市"],["山西医科大学第一医院","王育生","中国","山西省","太原市"],["湖南省肿瘤医院","刘振洋","中国","湖南省","长沙市"],["广西医科大学附属肿瘤医院","李永强","中国","广西壮族自治区","南宁市"],["复旦大学附属中山医院厦门医院","张博恒","中国","福建省","厦门市"],["南方医科大学南方医院","郭亚兵","中国","广东省","广州市"],["Westmead Hospital","Nagrial, Adnan","澳大利亚","Sydney","Sydney"],["Alfred Health","Gill, Sanjeev","澳大利亚","Melbourne","Melbourne"],["Austin Health","Tebbutt, Niall","澳大利亚","Melbourne","Melbourne"],["One Clinical Research","Khattak, Muhammad","澳大利亚","Perth","Perth"],["QEII Health Sciences Centre – Victoria General Site","Ramjeesingh, Ravi","加拿大","Halifax","Halifax"],["McGill University Health Centre","Mandilaras, Victoria","加拿大","Montreal","Montreal"],["Sunnybrook Research Institute - Odette Cancer Centre","Perera, Sheron","加拿大","Toronto","Toronto"],["Bradfordhill","Pizarro Brito, Gonzalo","智利","Santiago","Santiago"],["Fundacion Arturo Lopez Perez","Caglevic, Christian","智利","Santiago","Santiago"],["Clínica UC San Carlos de Apoquindo","Mondaca, Sebastian","智利","Santiago","Santiago"],["James Lind Centro de Investigacion del Cancer","Yanez Weber, Patricio","智利","Temuco","Temuco"],["Centro de Oncología de Precisión","Garrido, Marcelo","智利","Santiago","Santiago"],["Hopital Beaujon","Bouattour, Mohamed","法国","Clichy","Clichy"],["Centre Eugène Marquis Rennes - Centre de Lutte Contre le Cancer","Edeline, Julien","法国","Rennes","Rennes"],["Hopital de la Croix Rousse","MERLE, Philippe","法国","Lyon","Lyon"],["Sourasky Medical Center","Geva, Ravit","以色列","Tel Aviv","Tel Aviv"],["Hadassah Medical Center","Hubert, Ayala","以色列","Jerusalem","Jerusalem"],["Rambam Health Care Campus","Passhak, Maria","以色列","Haifa","Haifa"],["Fondazione IRCCS Istituto Nazionale dei Tumori","Pietrantonio, Filippo","意大利","Milano","Milano"],["ASST Grande Ospedale Metropolitano Niguarda","Siena, Salvatore","意大利","Milano","Milano"],["Fondazione Policlinico Universitario Agostino Gemelli","Tortora, Giampaolo","意大利","Roma","Roma"],["Harbour Cancer & Wellness","Deva, Sanjeev","新西兰","Auckland","Auckland"],["Seoul National Hospital","Oh, Do-Youn","韩国","Seoul","Seoul"],["Samsung Medical Center","Park, Joon Oh","韩国","Seoul","Seoul"],["Asan Medical Center","Kim, Tae Won","韩国","Songpagu","Songpagu"],["Severance Hospital, Yonsei University Health System","Beom, Seung-Hoon","韩国","Seodaemun-Gu","Seodaemun-Gu"],["Hospital Universitari Vall d'Hebron","Castet, Florian","西班牙","Barcelona","Barcelona"],["Hospital Central de Asturias","Jimenez Fonseca, Paula","西班牙","Oviedo","Oviedo"],["Hospital Universitario Gregorio Maranon","Munoz Martin, Andres Jesús","西班牙","Madrid","Madrid"],["Hospital Clinico San Carlos","Sastre Valera, Javier","西班牙","Madrid","Madrid"],["Hopitaux Universitaires de Geneve HUG.","Kossler, Thibaud","瑞士","Geneve","Geneve"],["Universitaetsspital Zuerich","Fritsch, Ralph","瑞士","Zurich","Zurich"],["National Taiwan University Hospital","Hsu, Chih-Hung","中国台湾","台北","台北"],["Taipei Veterans General Hospital","Chen, Ming-Huang","中国台湾","台北","台北"],["National Cheng Kung University Hospital","Yen, Chia-Jui","中国台湾","Tainan","Tainan"],["Faculty of Medicine Siriraj Hospital","Danchaivijitr, Pongwut","泰国","Bangkok","Bangkok"],["Ramathibodi Hospital","Ngamphaiboon, Nuttapong","泰国","Bangkok","Bangkok"],["Dr. Abdurrahman Yurtaslan Ankara Onkoloji Egitim ve Arast？rma Hastanesi","Karacin, Cengiz","土耳其","Ankara","Ankara"],["Hacettepe Universite Hastaneleri","Dizdar, Omer","土耳其","Ankara","Ankara"],["Dokuz Eylul Universitesi Hastanesi","Yavuzsen, Tugba","土耳其","Izmir","Izmir"],["Adana City Hospital","Cil, Timucin","土耳其","Adana","Adana"],["University of Colorado Cancer Center","Davis, Sarah","美国","CO","Aurora"],["University of Rochester","Dunne, Richard","美国","NY","Rochester"],["UF Health Davis Cancer Pavilion and Shands Med Plaza","George, Thomas","美国","FL","Gainesville"],["University of Chicago Medical Center","Amin, Manik","美国","IL","Chicago"],["Oncology and Hematology Associates of Southwest Virginia (BRCC)","Kochenderfer, Mark","美国","VA","Roanoke"],["Johns Hopkins University","Pishvaian, Michael","美国","MD","Baltimore"],["University of Wisconsin","Uboha, Nataliya","美国","WI","Madison"],["Perlmutter NYU Cancer Center","Beri, Nina","美国","NY","New York"],["Mount Sinai Cancer Center","Cusnir, Mike","美国","FL","Miami Beach"],["Hartford Hospital","Thumar, Jaykumar","美国","CT","Hartford"],["Rutgers Cancer Institute of New Jersey","Boland, Patrick","美国","NJ","New Brunswick"],["University of Missouri Hospital","Naha, Kushal","美国","MO","Columbia"],["Renown Regional Medical Center","Menon, Harry","美国","NV","Reno"],["Banner Gateway Medical Center","Gomez, Christina","美国","AZ","Gilbert"],["Scott & White Medical Center-Temple","Wong, Lucas","美国","TX","Temple"],["Stanford Cancer Institute","Heestand, Gregory","美国","CA","Stanford"]]

序号	机构名称	主要研究者	国家	省（州）	城市

[["复旦大学附属中山医院医学伦理委员会","修改后同意","2024-11-15"]]

序号	名称	审查结论	批准日期/备案日期

进行中（尚未招募）

目标入组人数	国内: 22 ； 国际: 130 ；
已入组人数	国内: 登记人暂未填写该信息； 国际: 7 ；
实际入组总人数	国内: 登记人暂未填写该信息； 国际: 登记人暂未填写该信息；

第一例受试者签署知情同意书日期	国内：登记人暂未填写该信息；     国际：2024-11-03；
第一例受试者入组日期	国内：登记人暂未填写该信息；     国际：2024-11-19；
试验完成日期	国内：登记人暂未填写该信息；     国际：登记人暂未填写该信息；