中国临床试验注册中心 - 世界卫生组织国际临床试验注册平台一级注册机构

注册号： Registration number：	ChiCTR1800014425
最近更新日期： Date of Last Refreshed on：	2018-01-12 20:21:50
注册时间： Date of Registration：	2018-01-12 00:00:00
注册号状态：	补注册
Registration Status：	Retrospective registration
注册题目：	重组全人抗PD-1单克隆抗体注射液治疗晚期实体瘤患者的I期临床研究
Public title：	A Phase I Study of Recombinant Human Anti-PD-1 Monoclonal Antibody for Patients With Advanced Solid Tumors
注册题目简写：
English Acronym：
研究课题的正式科学名称：	重组全人抗PD-1单克隆抗体注射液治疗晚期实体瘤患者的安全性、耐受性、药代动力学及抗肿瘤疗效的I期临床研究
Scientific title：	A Phase I Study to Investigate the Safety, Tolerability, Pharmacokinetics and Antitumor Activities of the Recombinant human anti-PD-1 Monoclonal Antibody for Subjects with Advanced Solid Tumors
研究课题代号(代码)： Study subject ID：
在二级注册机构或其它机构的注册号： The registration number of the Partner Registry or other register：

申请注册联系人：	刘振	研究负责人：	李国春
Applicant：	Liu Zhen	Study leader：	Li Guochun
申请注册联系人电话： Applicant telephone：	+86 18612920379	研究负责人电话： Study leader's telephone：	+86 010-68002437
申请注册联系人传真： Applicant Fax：	+86 010-68002438	研究负责人传真： Study leader's fax：
申请注册联系人电子邮件： Applicant E-mail：	yanfaliuzhen@gloria.cc	研究负责人电子邮件： Study leader's E-mail：	yanfazhongxin@gloria.cc
申请单位网址(自愿提供)： Applicant website(voluntary supply)：		研究负责人网址(自愿提供)： Study leader's website(voluntary supply)：
申请注册联系人通讯地址：	北京市顺义区空港开发区B区裕华路融慧园28号楼	研究负责人通讯地址：	北京市顺义区空港开发区B区裕华路融慧园28号楼
Applicant address：	28th Building, Ronghui Garden, Yuhua Road, Airport Development Zone B, Shunyi District, Beijing, China	Study leader's address：	28th Building, Ronghui Garden, Yuhua Road, Airport Development Zone B, Shunyi District, Beijing, China
申请注册联系人邮政编码： Applicant postcode：		研究负责人邮政编码： Study leader's postcode：
申请人所在单位：	哈尔滨誉衡药业股份有限公司
Applicant's institution：	Harbin Gloria Pharmaceuticals Co., Ltd.
研究负责人所在单位：
Affiliation of the Leader：

是否获伦理委员会批准：	是
Approved by ethic committee：	Yes
伦理委员会批件文号： Approved No. of ethic committee：	2017YW17	伦理委员会批件附件： Approved file of Ethical Committee：
批准本研究的伦理委员会名称：	北京肿瘤医院伦理委员会
Name of the ethic committee：	Ethics Committee of Beijing Cancer Hosptial
伦理委员会批准日期： Date of approved by ethic committee：	2017-04-24 00:00:00
伦理委员会联系人：	陆婷
Contact Name of the ethic committee：	Lu Ting
伦理委员会联系地址：	北京市海淀区阜成路81号1号楼5层
Contact Address of the ethic committee：	Fifth Floor, Building 1, 81 Fucheng Road, Haidian District, Beijing, China
伦理委员会联系人电话： Contact phone of the ethic committee：		伦理委员会联系人邮箱： Contact email of the ethic committee：

研究实施负责（组长）单位：

北京肿瘤医院

Primary sponsor：

Beijing Cancer Hosptical

研究实施负责（组长）单位地址：

北京市海淀区阜成路52号

Primary sponsor's address：

52 Fucheng Road, Haidia District, Beijing, China.

试验主办单位(项目批准或申办者)：

Secondary sponsor：

国家：	中国	省(直辖市)：	黑龙江	市(区县)：
Country：	China	Province：	Heilongjiang	City：
单位(医院)：	哈尔滨誉衡药业股份有限公司	具体地址：	黑龙江省哈尔滨市利民经济技术开发区北京路29号
Institution hospital：	Harbin Gloria Pharmaceuticals Co., Ltd.	Address：	29 Beijing Road, Limin Economic and Technological Development Zone, Harbin, Heilongjiang

经费或物资来源：

哈尔滨誉衡药业股份有限公司

Source(s) of funding：

Harbin Gloria Pharmaceuticals Co., Ltd.

研究疾病：

肿瘤

Target disease：

Tumor

研究疾病代码：

Target disease code：

研究类型：

观察性研究

Study type：

Observational study

研究所处阶段：

I期临床试验

Study phase：

1

研究设计：

非随机对照试验

Study design：

Non randomized control

研究目的：

剂量爬坡研究：主要目的：研究GLS-010在晚期实体瘤患者（以胃癌、食管癌为主）中的安全性和耐受性次要目的：研究GLS-010的药代动力学（PK）特点探索GLS-010的剂量限制性毒性（DLT）、最大耐受剂量（MTD）及推荐II期剂量（RP2D）初步探索GLS-010的抗肿瘤疗效探索评估GLS-010的程序性死亡因子1（PD-1）受体占有率探索性目的：初步探索程序性死亡因子受体1（PD-L1）/PD-L2表达情况与疗效的相关性评估GLS-010的免疫原性扩展研究：主要目的：初步研究GLS-010在晚期实体瘤患者(以胃癌、食管癌为主)中的抗肿瘤疗效次要目的：进一步评价GLS-010的安全性和耐受性探索性目的：评估PD-L1/PD-L2表达情况与疗效的相关性评估GLS-010的免疫原性

Objectives of Study：

Dose escalation study: Primary purpose: To investigate the safety and tolerability of GLS-010 in subjects with advanced solid tumors (mainly gastric cancer, esophageal cancer). Secondary purpose: 1. To characterize the pharmacokinetics(PK) profile of GLS-010; 2. To determine dose-limiting toxicity(DLT), maximum tolerated dose (MTD) and recommended Phase II dose (RP2D) for GLS-010; 3. To assess the preliminary anti tumor activity of GLS-010; 4. To assess programmed cell death-1 (PD-1) receptor occupancy. Exploratory purpose: 1. To investigate the preliminary relationship between the expression of the ligand of PD-1 (PD-L1) /PD-L2 and efficacy; 2. To characterize immunogenicity of GLS-010. Expansion study: Primary purpose: To assess the preliminary anti-tumor activity of GLS-010 in subjects with advanced solid tumors(gastric cancer, esophageal cancer); Secondary purpose: 1. To further assess the safety and tolerability of GLS-010; 2. To further assess the safety and tolerability of GLS-010 in subjects with advanced tumors. Exploratory purpose: 1. To assess PD-1 receptor occupancy of GLS-010; 2. To assess the relationship between the expression of PD-L1/PD-L2 and efficacy; 3. To further assess the immunogenicity of GLS-010.

药物成份或治疗方案详述：

Description for medicine or protocol of treatment in detail：

纳入标准：

Inclusion criteria

Subjects meet the following corresponding requirements for the stage of the study they will enroll into:
1. Subjects have voluntarily agreed to participate in the study; Fully understand and know the study and sign the informed consent; Willing to follow and be able to complete all procedures;
2. Male or female, and aged 18 to 75 years (including 18 and 75 years);
3. Subjects must have an imaging and histologically or cytologically confirmed advanced solid tumor;
Dose escalation study: Subjects with advanced solid tumor (mainly gastric cancer, esophageal cancer)
Expansion study: Patients with gastric cancer and esophageal cancer are expected to be enrolled which determine by the results of the dose escalation study;
4. Subjects must have archival tumor tissues or agree to a tumor biopsy during screening period. 
5. Subjects have no standard effective treatment or are ineffective with standard treatment.
6. Subjects must have at least one measurable lesion as defined per RECIST Version 1.1.
7. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1;
8. Life expectancy ≥12 weeks;
9. Subject must have adequate organ function and hematopoietic function indicated by the following laboratory values: Hemoglobin (HGB)≥90 g/L; White blood cell count (WBC)≥3×10^9/L; Absolute neutrophil count (ANC) ≥1.5×10^9/L; Platelets ≥100×10^9/L; Serum total bilirubin (TBIL) ≤ 1.5 *upper limit of normal ULN; Aspartate aminotransferase (AST) and alanine aminotransferase (ALT)≤2.5 X ULN OR ≤5 X ULN for subjects with liver metastases; Serum creatinine ≤1.5*ULN;	International Normalized Ratio (INR) or Prothrombin Time (PT) ≤1.5*ULN.
10. Childbearing potential female subjects or male subjects must agree to use adequate contraception after signing informed consent, and throughout the study until 5 months after the last GLS-010 administration.

排除标准：

符合以下任何一项的受试者不能入组本研究：
1) 有脑膜转移或有症状的中枢神经系统转移者；
2) 有症状的自身免疫性疾病的受试者（如以下，但不局限于：间质性肺炎，葡萄膜炎，肠炎，肝炎，垂体炎，血管炎，肾炎，甲状腺功能亢进，甲状腺功能降低[放疗导致的甲状腺功能降低可纳入]；受试者患有白癜风或在童年期哮喘已完全缓解，成人后无需任何干预的可纳入；受试者需要支气管扩张剂进行医学干预的哮喘则不能纳入）；
3) 入组前14天内或研究期间需要接受全身用皮质类固醇（剂量相当于或高于10 mg/天强的松）或其他免疫抑制药物治疗的受试者；
4) 接种过抗肿瘤疫苗者，或筛选前4周内曾接受过具有免疫刺激作用的抗肿瘤药治疗者；
5) 曾经用过抗PD-1抗体、抗PD-L1抗体、抗PD-L2抗体、抗CD137抗体或抗淋巴细胞抗原4（CTLA-4）抗体治疗（包括Ipilimumab或特异性作用于T细胞协同刺激或检查点途径的任何其他抗体或药物）；
6) 在入组前5年内罹患其他恶性肿瘤者，除了接受过适当治疗的宫颈原位癌、痊愈的皮肤基底细胞癌；
7) 乙肝表面抗原（HBsAg）阳性且乙肝病毒的脱氧核糖核酸（HBV DNA）> 103copies/ mL者，或丙型肝炎病毒抗体阳性者；梅毒阳性者；
8) 有感染人类免疫缺陷病毒病史，或患有其他获得性、先天性免疫缺陷疾病，或有器官移植史；
9) 通过病史或CT检查发现有活动性肺结核感染，或入组前1年内有活动性肺结核感染病史的患者，或超过1年以前有活动性肺结核感染病史但未经正规治疗的患者；
10) 受试者有活动性感染或在筛选期间、首次给药前发生原因不明发热> 38.5°C（经研究者判断，受试者因肿瘤产生的发热可以入组）；
11) 已知受试者既往对大分子蛋白制剂/单克隆抗体，或已知对任何试验药物组成成分过敏者；
12) 入组前4周内参加过其他药物临床试验；
13) 入组前2周内接受过化疗、放疗、分子靶向治疗或大型手术治疗；之前治疗相关的具有临床意义的AE还未恢复至基线或≤ 1级（脱发除外）；
14) 有未能良好控制的心脏临床症状或疾病，如未控制的高血压、不稳定心绞痛或试验入组前6个月内发生心肌梗塞、或控制不佳的心律失常（包括QTc间期男性≥ 450 ms、女性≥ 470 ms，QTc间期以Fridericia公式计算）等；
15) 间质性肺病或非感染性肺炎史（放射疗法引起的除外）；
16) 近1年内有酗酒，吸毒或药物滥用史；
17) 既往有明确的神经或精神障碍史，如癫痫、痴呆，依从性差者；
18) 研究者认为由于其他原因不适合参加该试验的受试者。

Exclusion criteria：

Subjects meet any of the following corresponding requirements for the stage of the study they will not enroll into:
1. Patients with meningeal or symptomatic central nervous system metastases;
2. Subjects with symptomatic autoimmune diseases(including but not limited to interstitial pneumonia, uveitis, enteritis, hepatitis, hypophysitis, vasculitis, nephritis, hyperthyroidism, hypothyroidism[except for hypothyroidism caused by radiotherapy], Subjects with vitiligo or asthma in childhood had been completely relieved, and no intervention was required when they grow to manhood can be enrolled in, subjects who needed bronchial dilation for medical intervention were not enrolled in);
3. Subjects who require systemic corticosteroids (at doses equivalent to or greater than 10 mg/day of prednisone) or other immunosuppressive drugs within 14 days prior to or during the study;
4. Subjects who have received anti-tumor vaccine or who have received anti-tumor drug treatment with immune-stimulating effect within 4 weeks before screening;
5. Subjects who have been treated with anti-PD-1 antibody, anti-PD-L1 antibody, anti-PD-L2 antibody, anti-CD137 antibody or anti-lymphocyte antigen 4 (CTLA-4) antibody (including ipilimumab or any other antibody or drug specifically acting on a T cell co-stimulatory or checkpoint pathway);
6. In addition to treated cervical carcinoma in situ and recovered skin basal cell carcinoma, other malignant tumors developed within 5 years prior to administration;
7. Subjects with positive HBsAg and HBV DNA>103 copies /mLor subjects with positive hepatitis C antibody; subjects with positive syphilis;
8. Subjects with a history of infection with human immunodeficiency virus, or other acquired, congenital immunodeficiency disease, or organ transplantation;
9. Subjects with active tuberculosis infection or active tuberculosis infection within 1 year prior to administration, or subjects with active tuberculosis infection more than 1 year prior to administration without formal treatment;
10. Subjects with active infection or unexplained fever >38.5℃ during screening and prior to first administration (subject with fever caused by tumor may be included in the group as determined by the investigator);
11. Known subjects who have previously been allergic to macromolecular protein formulations/monoclonal antibodies or to any of the pharmaceutical ingredients tested;
12. Subjects having participated in clinical trials of other drugs within 4 weeks before administration;
13. Subjects who received chemotherapy, radiotherapy, molecular targeted therapy or large-scale surgical treatment within 2 weeks before administration; Clinically significant AEs associated with previous treatment have not restored to baseline or ≤1 (except for alopecia);
14. Subjects who have failed to control the clinical symptoms or diseases of the heart, such as uncontrolled hypertension, unstable angina pectoris or subjects who have myocardial infarction within 6 months before administration, or subjects who have poor control of arrhythmia ( including QTc interval male ≥450 ms, women ≥470 ms, QTc interval calculated by Fridericia formula), etc.;
15. Subjects who have history of interstitial lung disease or non-infectious pneumonia (other than those caused by radiotherapy).
16. Subjects who have a history of alcoholism, drug abuse or drug abuse in the past 1 year;
17. Subjects who have a clear history of neurological or psychiatric disorders, such as epilepsy, dementia, and have poor compliance;
18. The investigators found that subjects who were not suitable for the trial for other reasons.

研究实施时间：

Study execute time：

从 From 2017-07-01 00:00:00至 To 2020-07-01 00:00:00

征募观察对象时间：

Recruiting time：

从 From 2017-07-10 00:00:00 至 To 2020-01-01 00:00:00

干预措施：

Interventions：

组别：	爬坡和扩展研究	样本量：	400
Group：	chort	Sample size：	400
干预措施：	GLS-010	干预措施代码：
Intervention：	GLS-010	Intervention code：

研究实施地点：

Countries of recruitment and research settings：

国家：	中国	省(直辖市)：	北京市	市(区县)：
Country：	China	Province：	Beijing	City：
单位(医院)：	北京肿瘤医院	单位级别：	三甲
Institution hospital：	Beijing Cancer Hospital	Level of the institution：	Tertiary A hospital

国家：	中国	省(直辖市)：	广州	市(区县)：
Country：	China	Province：	Guangzhou	City：
单位(医院)：	中山大学肿瘤防治中心	单位级别：	三甲
Institution hospital：	Sun Yat-sen University Cancer Center	Level of the institution：	Tertiary A hospital

国家：	中国	省(直辖市)：	上海	市(区县)：
Country：	China	Province：	Shanghai	City：
单位(医院)：	复旦大学肿瘤医院	单位级别：	三甲
Institution hospital：	Fudan University Cancer Hospital	Level of the institution：	Tertiary A hospital

测量指标：

Outcomes：

指标中文名：	安全性和耐受性	指标类型：	主要指标
Outcome：	Safety and Tolerance	Type：	Primary indicator
测量时间点：		测量方法：
Measure time point of outcome：		Measure method：

指标中文名：	初步抗肿瘤疗效	指标类型：	主要指标
Outcome：	Preliminary antitumor effect	Type：	Primary indicator
测量时间点：		测量方法：
Measure time point of outcome：		Measure method：

采集人体标本：

Collecting sample(s)
from participants：

标本中文名：	血液	组织：	肿瘤
Sample Name：	Blood	Tissue：	Tumor
人体标本去向	其它	说明
Fate of sample：	0thers	Note：

征募研究对象情况：

Recruiting status：

正在进行

Recruiting

年龄范围：

Participant age：

最小 Min age	18	岁 years
最大 Max age	75	岁 years

性别：

男女均可

Gender：

Both

随机方法（请说明由何人用什么方法产生随机序列）：

非随机研究

Randomization Procedure (please state who generates the random number sequence and by what method)：

non-randomized

是否公开试验完成后的统计结果:

Calculated Results after the Study Completed public access:

不公开/Private

盲法：
Blinding：

是否共享原始数据： IPD sharing	是Yes
共享原始数据的方式（说明：请填入公开原始数据日期和方式，如采用网络平台，需填该网络平台名称和网址）：	临床试验公共管理平台
The way of sharing IPD”(include metadata and protocol, If use web-based public database, please provide the url)：	ResMan
数据采集和管理（说明：数据采集和管理由两部分组成，一为病例记录表(Case Record Form, CRF)，二为电子采集和管理系统(Electronic Data Capture, EDC)，如ResMan即为一种基于互联网的EDC：	电子采集和管理系统
Data collection and Management (A standard data collection and management system include a CRF and an electronic data capture：	EDC
数据与安全监察委员会： Data and Safety Monitoring Committee：	无/No
注册人： Name of Registration：	2018-01-12 20:21:50