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：	ChiCTR2400083420
最近更新日期： Date of Last Refreshed on：	2024-04-24 15:45:00
注册时间： Date of Registration：	2024-04-24 00:00:00
注册号状态：	补注册
Registration Status：	Retrospective registration
注册题目：	评价YY001治疗晚期实体瘤患者的安全性、耐受性、药代动力学特征的开放性I期临床研究
Public title：	An Open-Label Phase I Study to Evaluate the Safety,Tolerability and Preliminary Efficacy of YY001 in Patients with Advanced Solid Tumors
注册题目简写：
English Acronym：
研究课题的正式科学名称：	评价YY001治疗晚期实体瘤患者的安全性、耐受性、药代动力学特征的开放性I期临床研究
Scientific title：	An Open-Label Phase I Study to Evaluate the Safety,Tolerability and Preliminary Efficacy of YY001 in Patients 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：	王金花	研究负责人：	郭晔
Applicant：	Wang Jinhua	Study leader：	Guo Ye
申请注册联系人电话： Applicant telephone：	+86 198 2273 0520	研究负责人电话： Study leader's telephone：	+86 135 0167 8472
申请注册联系人传真： Applicant Fax：		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：	wangjh@yuyaobiotech.com	研究负责人电子邮件： Study leader's E-mail：	pattrickguo@gmail.com
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：	上海市闵行区潭竹路58号1幢1001室	研究负责人通讯地址：	上海市浦东新区云台路1800号
Applicant address：	58 Tanzhu Road, Building 1, Room 1001, Minhang, Shanghai 200241, China	Study leader's address：	1800 Yuntai Road, Pudong New Area, Shanghai, 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：	上海宇耀生物科技有限公司
Applicant's institution：	Shanghai Yuyao Biotech Co., Ltd.
研究负责人所在单位：	上海市东方医院
Affiliation of the Leader：	Shanghai East Hospital

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：	[2022]临审第(029)号	伦理委员会批件附件： Approved file of Ethical Committee：	查看附件View
批准本研究的伦理委员会名称：	上海市东方医院药物临床试验伦理委员会
Name of the ethic committee：	Shanghai Dongfang Hospital Clinacal Trila Ethics Committee
伦理委员会批准日期： Date of approved by ethic committee：	2022-05-20 00:00:00
伦理委员会联系人：	鲍思蔚
Contact Name of the ethic committee：	Bao Siwei
伦理委员会联系地址：	上海市浦东新区云台路1800号
Contact Address of the ethic committee：	1800 Yuntai Road, Pudong New Area, Shanghai
伦理委员会联系人电话： Contact phone of the ethic committee：	+86 21 3880 4518	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：

上海市东方医院

Primary sponsor：

Shanghai East Hospital

研究实施负责（组长）单位地址：

上海市浦东新区云台路1800号

Primary sponsor's address：

1800 Yuntai Road, Pudong New District, Shanghai

试验主办单位(项目批准或申办者)：

Secondary sponsor：

国家：	中国	省(直辖市)：	上海市	市(区县)：
Country：	China	Province：	Shanghai	City：
单位(医院)：	上海宇耀生物科技有限公司	具体地址：	上海市闵行区潭竹路58号1幢1001室
Institution hospital：	Shanghai Yuyao Biotech Co., Ltd.	Address：	58 Tanzhu Road, Building 1, Room 1001, Minhang, Shanghai 200241, China

经费或物资来源：

上海宇耀生物科技有限公司

Source(s) of funding：

Shanghai Yuyao Biotech Co., Ltd.

研究疾病：

晚期实体瘤

Target disease：

Advanced solid tumors

研究疾病代码：

Target disease code：

研究类型：

干预性研究

Study type：

Interventional study

研究所处阶段：

I期临床试验

Study phase：

1

研究设计：

单臂

Study design：

Single arm

研究目的：

主要目的：评价YY001治疗晚期实体瘤患者的安全性、耐受性，观察可能出现的剂量限制性毒性（DLT）及最大耐受剂量（MTD）或推荐II期临床给药剂量（RP2D）。次要目的：评价YY001在晚期实体瘤患者中的药代动力学（PK）特征和抗肿瘤活性。探索性目的：初步评价生物标志物与疗效之间的关系。

Objectives of Study：

Primary Objectives: The safety and tolerability of YY001 in the treatment of patients with advanced solid tumors were evaluated, and the possible dose-limiting toxicity (DLT) and the maximum tolerated dose (MTD) or recommended phase II clinical dose (RP2D) were observed. Secondary objectives: To evaluate the pharmacokinetics (PK) and antitumor activity of YY001 in patients with advanced solid tumors. Exploratory purpose: The relationship between the preliminary evaluation of biomarkers and curative effect.

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

1.Patients fully understand and sign ICF, voluntarily participate in the study, and able to follow and complete all study procedures.
2. Aged 18-75 years (including upper and lower limits), male or female.
3. Patients with histologically or cytologically confirmed advanced unresectable or metastatic solid tumors (mainly gastrointestinal tumors such as colorectal cancer and gastric cancer, and prostate cancer)
4.The standard treatment failure (disease progression after treatment or treatment side effects not tolerance), or top treatment, or shall not apply to the current standard treatment for patients 
5. For patients with advanced solid tumors (dose-escalation phase), at least one tumor lesion that could be evaluated according to RECIST, version 1.1; (Dose-expansion phase) At least one measurable tumor lesion according to RECIST, version 1.1 (a tumor that is located in the previously irradiated area or another locoregional treatment site and is generally not considered a measurable lesion unless there is definite progression or persistence beyond 3 months of radiation);
6. ECOG physical condition≤1
7. Patients with advanced primary liver cancer should meet the Child-Pugh liver function grading: grade A and better grade B (≤7).
8. With adequate bone marrow, liver and kidney organ function:
Blood system within 14 days (not received blood transfusions or hematopoietic stimulating factor treatment)
Absolute neutrophil count (ANC) ≥1.5×10^9/L
Platelet count (PLT) ≥75×10^9/L
Hemoglobin (Hb) ≥85g/L
Liver function
Total bilirubin (TBIL) ≤1.5×ULN
Alanine aminotransferase (ALT) ≤3×ULN;
Spread to the liver or liver cancer patient: 5 or less x ULN
Aspartate aminotransferase (AST) or less 3 x ULN.
Spread to the liver or liver cancer patient: 5 or less x ULN
Renal function
Creatinine (Cr) or less 1.5 x ULN
Creatinine clearance (Ccr) (calculated only when creatinine > 1.5× ULN) ≥50ml/min (calculated according to Cockcroft-Gault formula)
Blood coagulation function
Activated partial thromboplastin time (APTT) ≤1.5×ULN
International normalized ratio (INR) ≤1.5×ULN
Urinary protein
Urine routine /24 hours urine protein qualitative ≤1+;
Or urine protein qualitative ≥2+, 24 hours urine protein < 1g
9. Expected survival of at least 3 months.
10. Women of childbearing potential had to have a negative serum or urine pregnancy test within 7 days before the first dose. Fertile male or female patients voluntarily during the study period and at the end of the study drug within 30 days of using effective birth control methods, such as abstinence, the double protective screen type cuts, condoms, contraceptive method of oral or injected contraceptives, intrauterine device, etc. All female patients will be considered fertile unless the female patient has undergone natural menopause, artificial menopause, or sterilization (e.g., hysterectomy, bilateral adnophorectomy, or radioactive ovarian irradiation).

排除标准：

1. 既往抗肿瘤治疗的不良反应尚未恢复到CTCAE 5.0等级评价≤1级（研究者判断无安全风险的毒性除外，如脱发、2级外周神经毒性、经激素替代治疗稳定的甲状腺功能减退等）； 2. 具有临床症状的脑实质转移或脑膜转移，经研究者判断不适合入组； 3. 首次给药前4周内接受过化疗、放疗、生物治疗、内分泌治疗、免疫治疗等抗肿瘤药物治疗，除外以下几项： • 亚硝基脲或丝裂霉素C为首次使用研究药物前6周内； • 口服氟尿嘧啶类和小分子靶向药物为首次使用研究药物前2周或药物的5个半衰期内（以时间长的为准）； • 有抗肿瘤适应症的中药为首次使用研究药物前2周内。 4. 首次给药前4周内接受过其它未上市的临床研究药物或治疗； 5. 既往接受过EP4拮抗剂（如AN0025（E7046）、LY3127760、ONO-4578）用于抗肿瘤治疗； 6. 首次用药前4周内接受过主要脏器外科手术（不包括穿刺活检），或需要在试验期间接受择期手术； 7. 不能控制的恶性胸水、腹水或心包积液，经研究者判断不适合入组； 8. 无法口服吞咽药物，或存在经研究者判断严重影响胃肠道吸收的状况，包括但不限于炎症性肠病等（例如克罗恩氏病、溃疡性结肠炎），或者吸收不良综合征，或者慢性腹泻； 9. 首次用药前1周内接受过CYP3A4强效诱导剂或抑制剂，或研究期间需要继续接受这些药物治疗的患者； 10. 患者目前存在胃及十二指肠活动性溃疡、溃疡性结肠炎等消化道疾病或未切除的肿瘤存在活动出血，或研究者判定的可能引起消化道出血、穿孔的其他状况； 11. 首次用药前12个月内发生过血栓栓塞事件（包括卒中事件和/或短暂性脑缺血发作）； 12. 有显著临床意义的心血管疾病，包括但不限于首次用药前6个月内急性心肌梗死、严重/不稳定心绞痛或者冠脉搭桥术；充血性心力衰竭纽约心脏协会（NYHA）分级≥2级；左心室射血分数（LVEF）<50%；原发性心肌病、有临床意义的QTc间期延长病史，或筛选期QTc 间期女性>470ms、男性>450ms； 13. 患有活动性、或曾患过且有复发可能的自身免疫性疾病的患者（如系统性红斑狼疮，类风湿性关节炎，血管炎等），除外临床稳定的自身免疫甲状腺病、I型糖尿病患者； 14. 曾接受免疫治疗并出现≥3级irAE或≥2级免疫相关性心肌炎； 15. 研究者判断有临床意义的≥3级的电解质异常； 16. 患者有活动性感染需要静脉抗感染治疗或在筛选期间、首次给药前发生原因不明的发热（体温 >38.5℃）； 17. 患有活动性肺结核（TB）的患者，正在接受抗结核治疗或者首次用药前1年内接受过抗结核治疗；已知的人类免疫缺陷病毒（HIV）感染；有乙肝肝炎病史患者处于活动性感染阶段（HBsAg阳性且HBV -DNA＞研究中心检测下限）；有丙型肝炎病史患者处于活动性感染阶段，定义为HCV抗体检测阳性且可检测到HCV RNA； 18. 妊娠（用药前妊娠检测阳性）或正在哺乳的女性； 19. 已知有酒精或药物依赖； 20. 精神障碍者或依从性差者； 21. 研究者认为受试者存在其他原因而不适合参加本临床研究。

Exclusion criteria：

1. The adverse reactions of previous antineoplastic therapy have not recovered to CTCAE 5.0 grade ≤1 (except for toxicities without safety risks judged by investigators, such as alopecia, grade 2 peripheral neurotoxicity, and hypothyroidism stable with hormone replacement therapy); 2. Clinically symptomatic parenchymal or leptomeningeal metastases that were judged by the investigator to be ineligible for enrollment; 3. Within 4 weeks before delivery for the first time received chemotherapy, radiation therapy, biological therapy and endocrine therapy, immune therapy, such as antitumor drugs, with the exception of the following situations: •Nitrosourea or mitomycin C within 6 weeks before first use of study drug; •Oral fluorouracils and small-molecule targeted agents are administered 2 weeks before first use of the study drug or within the five half-lives of the drug, whichever is longer; •Have antitumor indications for the study of the first use of drugs of traditional Chinese medicines before 2 weeks; 4. Received other unlisted investigational drugs or treatments within 4 weeks before the first dose; 5. Previously received EP4 inhibitor (e.g. AN0025(E7046),LY3127760,ONO-4578) for anti-tumor treatment; 6. Major organ surgery (excluding needle biopsy) within 4 weeks before the first dose of medication or requiring elective surgery during the trial; 7. Uncontrolled malignant pleural, ascites, or pericardial effusion that was judged by the investigator to be ineligible for enrollment; 8. Unable to oral drug swallowing, or by the researchers determine the condition of the seriously affect the gastrointestinal tract absorption, including but not limited to, such as inflammatory bowel disease (crohn's disease and ulcerative colitis, for example), or malabsorption syndrome, or chronic diarrhea; 9. Patients who received a potent inducer or inhibitor of CYP3A4 within 1 week before the first dose or who required continued treatment with these drugs during the study; 10. Patients with active gastric and duodenal ulcer, ulcerative colitis and other gastrointestinal diseases, or unresected tumor with active bleeding, or other conditions that may cause gastrointestinal bleeding or perforation as judged by the investigator; 11. Thromboembolic events (including stroke events and/or transient ischemic attack) occurred within 12 months before the first dose of medication; 12. Clinically significant cardiovascular disease, including but not limited to acute myocardial infarction, severe/unstable angina, or coronary artery bypass grafting within 6 months before the first dose of medication; Congestive heart failure with New York Heart Association (NYHA) grade ≥2; Left ventricular ejection fraction (LVEF) <50%; A history of primary cardiomyopathy, clinically significant prolongation of the QTc interval, or a screening QTc interval >470ms in women and >450ms in men; 13. Patients with active or previous autoimmune diseases with potential recurrence (such as systemic lupus erythematosus, rheumatoid arthritis, vasculitis, etc.), excluding patients with clinically stable autoimmune thyroid diseases and type I diabetes mellitus; 14. Prior immunotherapy with grade ≥3 irAE or grade ≥2 immune-related myocarditis; 15. Researchers to determine the clinical significance of 3 or more electrolyte abnormalities 16. Patients with active infection requiring antiinfective treatment or unexplained fever (body temperature >38.5 ° C) during screening or before the first dose of medication; 17. Patients with active pulmonary tuberculosis (TB) who were receiving anti-TB treatment or had received anti-TB treatment within 1 year before the first dose; Known human immunodeficiency virus (HIV) infection; Patients with a history of hepatitis B were in the stage of active infection (HBsAg positive and HBV-DNA > the detection limit of the research center); Patients with a history of hepatitis C were in the active infection stage, defined as positive HCV antibody test and detectable HCV RNA; 18. Women who are pregnant (positive pregnancy test within 14 days before medication) or are breastfeeding 19. Patients with known alcohol or drug dependence; 20. Patients judged by the investigator that may not be able to comply with all study procedures; 21. Any other disease, metabolic abnormality, abnormal physical examinations or laboratory abnormality with significant clinical significance. Investigator reasonably suspects that the patient has a disease or state that is not suitable for using of the study drug, or will affect interpretation of study results, or put the patient at high risk.

研究实施时间：

Study execute time：

从 From 2022-03-01 00:00:00至 To 2024-04-30 00:00:00

征募观察对象时间：

Recruiting time：

从 From 2022-07-14 00:00:00 至 To 2023-06-29 00:00:00

干预措施：

Interventions：

组别：	试验组1	样本量：	1
Group：	Test group 1	Sample size：	1
干预措施：	YY001片，100mg	干预措施代码：
Intervention：	YY001 tablets, 100mg	Intervention code：

组别：	试验组2	样本量：	1
Group：	Test group 2	Sample size：	1
干预措施：	YY001片，200mg	干预措施代码：
Intervention：	YY001 tablets, 200mg	Intervention code：

组别：	试验组3	样本量：	4
Group：	Test group 3	Sample size：	4
干预措施：	YY001片，300mg	干预措施代码：
Intervention：	YY001 tablets, 300mg	Intervention code：

组别：	试验组4	样本量：	3
Group：	Test group 4	Sample size：	3
干预措施：	YY001片，400mg	干预措施代码：
Intervention：	YY001 tablets, 400mg	Intervention code：

组别：	试验组5	样本量：	7
Group：	Test group 5	Sample size：	7
干预措施：	YY001片，500mg	干预措施代码：
Intervention：	YY001 tablets, 500mg	Intervention code：

研究实施地点：

Countries of recruitment and research settings：

国家：	中国	省(直辖市)：	上海市	市(区县)：	上海市
Country：	China	Province：	Shanghai	City：
单位(医院)：	上海市东方医院	单位级别：	三甲
Institution hospital：	Shanghai East Hospital	Level of the institution：	Tertiary A

国家：	中国	省(直辖市)：	安徽	市(区县)：	蚌埠
Country：	China	Province：	Anhui	City：
单位(医院)：	蚌埠医学院第一附属医院	单位级别：	三甲
Institution hospital：	The First Affiliated Hospital of Bengbu Medical College	Level of the institution：	Tertiary A

测量指标：

Outcomes：

指标中文名：	剂量限制性毒性	指标类型：	主要指标
Outcome：	Dose limiting toxicity	Type：	Primary indicator
测量时间点：		测量方法：
Measure time point of outcome：		Measure method：

指标中文名：	最大耐受剂量	指标类型：	主要指标
Outcome：	Maximum tolerated dose	Type：	Primary indicator
测量时间点：		测量方法：
Measure time point of outcome：		Measure method：

指标中文名：	安全性指标	指标类型：	主要指标
Outcome：	Safety index	Type：	Primary indicator
测量时间点：		测量方法：
Measure time point of outcome：		Measure method：

指标中文名：	疗效评价	指标类型：	次要指标
Outcome：	Evaluation of therapeutic efficiency	Type：	Secondary indicator
测量时间点：		测量方法：
Measure time point of outcome：		Measure method：

指标中文名：	药代动力学指标	指标类型：	次要指标
Outcome：	Pharmacokinetic index	Type：	Secondary indicator
测量时间点：		测量方法：
Measure time point of outcome：		Measure method：

指标中文名：	生物标志物	指标类型：	次要指标
Outcome：	Biomarker	Type：	Secondary indicator
测量时间点：		测量方法：
Measure time point of outcome：		Measure method：

指标中文名：	二期推荐给药剂量	指标类型：	主要指标
Outcome：	The recommended phase 2 dose	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：	肿瘤组织	组织：
Sample Name：	tumor tissue	Tissue：
人体标本去向	使用后销毁	说明
Fate of sample：	Destruction after use	Note：

标本中文名：	尿液	组织：
Sample Name：	urine	Tissue：
人体标本去向	使用后销毁	说明
Fate of sample：	Destruction after use	Note：

标本中文名：	血液	组织：
Sample Name：	Blood	Tissue：
人体标本去向	使用后销毁	说明
Fate of sample：	Destruction after use	Note：

征募研究对象情况：

Recruiting status：

结束

/Completed

年龄范围：

Participant age：

最小 Min age	18	岁 years
最大 Max age	80	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）：

无

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

None

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）：	文章发布后六个月上传至临床试验公共管理平台 (http://www.medresman.org.cn)
The way of sharing IPD”(include metadata and protocol, If use web-based public database, please provide the url)：	ResMan (http://www.medresman.org.cn).
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：	Electronic Data Capture, EDC
数据与安全监察委员会： Data and Safety Monitoring Committee：	有/Yes
注册人： Name of Registration：	2024-04-24 15:44:42