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：	ChiCTR2500102637
最近更新日期： Date of Last Refreshed on：	2025-05-16 17:04:56
注册时间： Date of Registration：	2025-05-16 00:00:00
注册号状态：	预注册
Registration Status：	Prospective registration
注册题目：	一项评价口服 YY2201片在晚期实体瘤患者中的安全性、耐受性、药代动力学以及初步抗肿瘤疗效的Ⅰ期剂量递增研究
Public title：	A Dose-escalation Phase I Study to Assess the Safety, Tolerability, Pharmacokinetics and Preliminary Anti-tumor Activity of YY2201 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：	一项评价口服 YY2201片在晚期实体瘤患者中的安全性、耐受性、药代动力学以及初步抗肿瘤疗效的Ⅰ期剂量递增研究
Scientific title：	A Dose-escalation Phase I Study to Assess the Safety, Tolerability, Pharmacokinetics and Preliminary Anti-tumor Activity of YY2201 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：	翟文姬	研究负责人：	张剑
Applicant：	Wenji Zhai	Study leader：	Jian Zhang
申请注册联系人电话： Applicant telephone：	+86 25 5813 8662	研究负责人电话： Study leader's telephone：	+86 21 6417 5590
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：	fanjihui@js.yayobio.com	研究负责人电子邮件： Study leader's E-mail：	syner2000@163.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：	南京市江北新区新锦湖路3-1号中丹生态生命科学产业园一期B座1602-1607室	研究负责人通讯地址：	上海市浦东新区康新公路4333号
Applicant address：	Room 1602-1607, Building B, Phase I, Zhongdan Ecological Life Science Industrial Park, No. 3-1 Xinjinhu Road, Jiangbei New Area, Nanjing, Jiangsu Province, China	Study leader's address：	No. 4333 Kangxin Road, Pudong New Area, Shanghai
申请注册联系人邮政编码： Applicant postcode：	210032	研究负责人邮政编码： Study leader's postcode：	200032
申请人所在单位：	江苏亚尧生物科技有限公司
Applicant's institution：	Jiangsu YaYao Biotechnology Co., Ltd.
研究负责人所在单位：	复旦大学附属肿瘤医院
Affiliation of the Leader：	Fudan University Shanghai Cancer Center

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：	2504318-15	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：	复旦大学附属肿瘤医院医学伦理委员会
Name of the ethic committee：	Medical Ethics Committee of Fudan University Shanghai Cancer Center
伦理委员会批准日期： Date of approved by ethic committee：	2025-04-18 00:00:00
伦理委员会联系人：	张玮静
Contact Name of the ethic committee：	weijing Zhang
伦理委员会联系地址：	中国上海市东安路270号复旦大学附属肿瘤医院2号楼2楼216室
Contact Address of the ethic committee：	Room 216, Building 2, Fudan University Shanghai Cancer Center, No. 270 Dongan Road, Shanghai, China
伦理委员会联系人电话： Contact phone of the ethic committee：	+86 21 6417 5590	伦理委员会联系人邮箱： Contact email of the ethic committee：	JJYIN555@163.com

研究实施负责（组长）单位：

复旦大学附属肿瘤医院

Primary sponsor：

Fudan University Shanghai Cancer Center

研究实施负责（组长）单位地址：

上海市浦东新区康新公路4333号

Primary sponsor's address：

No. 4333 Kangxin Road, Pudong New Area, 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)：	上海市
Country：	China	Province：	Shanghai	City：	Shanghai
单位(医院)：	复旦大学附属肿瘤医院	具体地址：	上海市浦东新区康新公路4333号
Institution hospital：	Fudan University Shanghai Cancer Center	Address：	No. 4333 Kangxin Road, Pudong New Area, Shanghai

经费或物资来源：

自筹

Source(s) of funding：

Self-funded

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：评估口服YY2201在晚期实体瘤患者中的安全性和耐受性；评估口服YY2201在晚期实体瘤患者中的最大耐受剂量（MTD）和/或II期推荐剂量（RP2D）；次要目的：评估YY2201在晚期实体瘤患者中的药代动力学（PK）特征；初步评估口服YY2201在晚期实体瘤患者中的抗肿瘤疗效。

Objectives of Study：

Main purpose: Evaluate the safety and tolerability of oral YY2201 in patients with advanced solid tumors; Evaluate the maximum tolerated dose (MTD) and/or phase II recommended dose (RP2D) of oral YY2201 in patients with advanced solid tumors; Secondary purpose: Evaluate the pharmacokinetic (PK) characteristics of YY2201 in patients with advanced solid tumors; Preliminary evaluation of the anti-tumor efficacy of oral YY2201 in patients with advanced solid tumors.

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

Research participants must meet all of the following inclusion criteria in order to be enrolled in this trial:
1. Voluntarily participate in clinical research and sign a written informed consent form, and be able to comply with the procedures related to clinical visits and research;
2. Men or women aged 18 or above who sign the informed consent form;
3. Patients with advanced solid tumors diagnosed by histology or cytology, who have failed standard treatment, have no standard treatment plan, or are currently not suitable for standard treatment;
4. The score of the Eastern Cooperative Oncology Group (ECOG) is 0 or 1;
5. Expected survival time is not less than 3 months;
6. The bone marrow reserve and organ function level must meet the following requirements (no supportive treatment such as blood components or growth factors received within 7 days prior to laboratory testing):
Bone marrow reserve: neutrophil count (ANC)>=1.5 × 10 ^ 9/L; platelet count (PLT)>=90 × 10 ^ 9/L; hemoglobin (HGB)>9.0 g/dL;
Coagulation function: International normalized ratio (INR) or prothrombin time (PT) and activated partial thromboplastin time (APTT)<=1.5 × ULN;
Liver function: Blood bilirubin (TBIL)<=1.5 × ULN; Alanine aminotransferase (ALT) and aspartate aminotransferase (AST)<=2.5 × ULN, and if there is liver metastasis, ALT or AST<=5 × ULN;
Renal function: creatinine clearance rate>=50 mL/min (using Cockcroft Gault formula) or serum creatinine<=1.5 × ULN;
Cardiac function: Left ventricular ejection fraction (LVEF)>=50%;
7. There is at least one measurable lesion (according to RECIST v1.1 standard);
8. Qualified subjects (male and female) with fertility must agree to use reliable contraceptive methods (such as hormones, barrier methods, or abstinence) with their partners for at least 3 months during the trial period and after the last use of medication; Female subjects of childbearing age must have a negative serum pregnancy test within 7 days prior to the first use of the investigational drug.

排除标准：

出现以下任何一种情况的受试者不得入组本试验： 1.在首次使用试验药物前28天内接受过抗肿瘤治疗（或接受过其它未上市的临床试验药物或治疗的5个半衰期内，以时间短的为准），除外以下几项： a)对于内分泌治疗、有抗肿瘤适应症的中药、化疗、小分子抗肿瘤药物，为了避免让患者等待过长时间，可以适当缩短清洗期至14天； b)对于有干扰的抗体类药物，在有必要的时候，需要适当延长洗脱期； 2.受试者既往（筛选前2年内）或同时患有其它恶性肿瘤（已治愈的皮肤基底细胞癌、宫颈原位癌、乳腺原位癌和不需要治疗的前列腺癌除外）； 3.在首次使用试验药物前4周内接受过主要脏器外科手术（不包括穿刺活检）或出现过显著外伤，或需要在试验期间接受择期手术； 4.正在服用（或在试验首次给药至少1周前不能够停用）任何已知强抑制或诱导CYP2C8和 CYP3A4的药物，抑制P-gp、BCRP的药物，或者是P-gp和BCRP底物的药物； 5.既往治疗的不良反应尚未恢复到≤1级（根据CTCAE 5.0），经研究者判断无安全风险的毒性除外（如脱发、2级外周神经的病变或功能障碍等）； 6.存在脊髓压迫或脑转移，除非无症状、经过治疗且稳定，并且在开始研究治疗前至少连续4周需要每天剂量超过10 mg的泼尼松或与其等效的持续性皮质类固醇治疗；存在软脑膜转移病史的受试者； 7.存在经研究者判断严重影响胃肠道吸收的状况，如难治性恶心和呕吐/肠梗阻/胃出口梗阻/无法吞咽制剂/既往曾接受重大胃肠道切除手术等； 8.首次使用试验药物前1周内存在活动性感染，且目前需要系统性抗感染治疗者； 9.乙肝表面抗原（HBsAg）阳性，且 HBV DNA﹥2000 IU/mL或104拷贝数/mL者，乙型肝炎病毒感染者应根据当地治疗指南标准接受抗病毒治疗且愿意在研究期间全程接受抗病毒治疗；丙肝抗体阳性，且HCV RNA 高于研究中心正常值上限；HIV感染；梅毒螺旋体抗体阳性； 10.有严重的心脑血管疾病史，包括但不限于：有严重的心脏节律或传导异常，如需要临床干预的室性心律失常、Ⅱ-Ⅲ度房室传导阻滞等，PR间期> 250 ms；需要治疗性抗凝的血栓栓塞事件，或具有静脉滤器的受试者；按美国纽约心脏病协会（NYHA）标准，III~IV级心功能不全者；首次给药前12个月内发生急性冠脉综合征、充血性心力衰竭、主动脉夹层、脑卒中或其他3级及以上心脑血管事件；经Fridericia公式计算校正的QT间期（QTcF）延长（男性 > 450ms，女性 > 470ms）；具有增加QTc延长风险和心律不齐风险的因素，如心衰、先天性长QT综合征、长QT综合征家族史、发生过任何伴随药物导致的QT间期延长； 11.已知有药物滥用史； 12.精神疾病障碍、认知或记忆力严重障碍、依从性差者，或其他经研究者判断有其它不适于参与研究的情况； 13.妊娠期或哺乳期女性； 14.无法耐受静脉采血者； 15.已知对YY2201或其任何辅料成分过敏； 16.研究者认为受试者存在其他严重的全身性疾病史、或其他原因而不适合参加本临床研究。

Exclusion criteria：

Patient who meets any of the following criteria should be excluded from this study: 1.Has received chemotherapy, radiotherapy, biological therapy, endocrine therapy, immune checkpoint inhibitor therapy, other anti-tumor treatments, or other un-marketed investigational drugs within 4 weeks prior to first dose of YY2201 (or within 5 half-lives of treatment, whichever is shorter), except for the following items: Have used nitrosourea or Mitomycin C within 6 weeks prior to first dose of Y2201. Have used oral fluorouracil and small molecule targeted drugs within 2 weeks or 5 half-lives of the drugs prior to first dose of YY2201 (whichever is longer). Have used herbal therapy with anti-tumor indications are within 2 weeks prior to first dose of YY2201. 2.Has prior (within 2 years before screening) or concurrent other malignancy (except for cured basal cell carcinoma of the skin, carcinoma in situs of cervix, ductal carcinoma in-situ, and prostate cancer which not requiring treatment). 3.Has undergone major organ surgery (excluding biopsy) or have had significant trauma within 4 weeks prior to first dose of YY2201 or required elective surgery during the study period. 4.Is taking (or cannot be stopped at least 1 week prior to first dose of YY2201) any drug that is known to strongly or moderately inhibit or induce CYP2C8 and CYP3A4. 5.The adverse reactions of previous anti-tumor treatments have not yet recovered to grade ≤1 (except for toxicity judged by the investigator to have no safety risk, such as alopecia and fantigue). 6.Has spinal cord compression or brain metastases and requiring corticosteroid therapy at a dose of more than 10 mg prednisone or equivalent per day for at least 4 consecutive weeks prior to initiation of study treatment (unless asymptomatic, treated, and stable) or a history of leptomeningeal metastases. 7.Any gastrointestinal tract related conditions that may affect the drug absorption as judged by the investigator, such as nausea and vomiting that are difficult to control, intestinal obstruction, gastric outlet obstruction, unable to swallow preparations, previous major gastrointestinal resection and so on. 8.Has active infection 1 week before the first dose of YY2201 and currently need systemic anti-infection treatment. 9.HIV infection, or active HBV infection or active HCV infection, with the exception: a) Patients with serologic evidence of chronic HBV infection and have HBV viral load below the limit of quantification with normal liver function. b) Patients with serologic evidence of HCV infection and have negative hepatitis C virus RNA test results. 10.History of serious cardiovascular and cerebrovascular diseases, including but not limited to: Severe cardiac rhythm or conduction abnormality, such as ventricular arrhythmia requiring clinical intervention, second-third degree atrioventricular block, etc., PR interval > 250 ms; Thromboembolic events requiring therapeutic anticoagulation, or subjects with a venous filter; Patients with Class III~IV cardiac insufficiency according to the criteria of New York Heart Association (NYHA); Acute coronary syndrome, congestive heart failure, aortic dissection, stroke or other grade 3 or higher cardiovascular and cerebrovascular events within 12 months prior to the first dose; QT interval corrected through Fridericia's formula (QTcF) prolongation (male > 450 ms, female > 470 ms); any factors that increase the risk of QTc prolongation and arrhythmia, such as heart failure, congenital long QT syndrome, family history of long QT syndrome, and QT interval prolongation caused by any concomitant drug. 11.History of non-infectious pneumonitis (NIP)/pneumonitis requiring systemic steroids, or active NIP/ pneumonitis, or other severe lung disease. 12.Substance use disorder that may interfere with the participant’s involvement in the study or evaluation of the study result, as determined by the investigator. 13.Patient with mental disorders, severe cognitive disorder, poor compliance, or is not suitable for participating in this clinical study determined by the Investigator. 14.Women who are pregnant or breastfeeding. 15.Patient who cannot tolerate venous blood sampling. 16.Known allergy to YY2201 or any of its excipient. 17.History of other serious systemic diseases, or not suitable to participate in this study for other reasons as judged by the Investigator.

研究实施时间：

Study execute time：

从 From 2025-05-26 00:00:00至 To 2027-10-11 00:00:00

征募观察对象时间：

Recruiting time：

从 From 2025-05-26 00:00:00 至 To 2027-10-11 00:00:00

干预措施：

Interventions：

组别：	试验组	样本量：	42
Group：	Experimental group	Sample size：	42
干预措施：	DLT评估期后，在研究期间，对尚未治疗结束的受试者，若研究者基于已获得的安全性和疗效数据，认为上调剂量可使其进一步获益，且与申办者沟通确认后，可对受试者的给药剂量进行上调。上调剂量必须为当前已由SMC投票通过的安全剂量，且应尽可能接近既定或预期的RP2D。研究期间发生AE时，必要时经研究者与申办者商议并一致同意后，可暂停或下调剂量使用试验药物，并采取最佳支持治疗。	干预措施代码：
Intervention：	No intra-subject dose escalation is allowed during the DLT observation period (C0D1~C1D21).After the DLT observation period, a subject may escalate to a dose level higher than the dose level they have been initially assigned to only if the discussion of Investigator and the sponsor and reach a consensus that intra-individual dose escalation would provide further benefit based on the available safety and efficacy data. The dose that escalated to must be a safe dose that has been voted on by the SMC and should be as close as possible to the established or expected RP2D. In the event of significant toxicity, dosing may be delayed and/or reduced and optimal supportive treatment should be taken if necessary.	Intervention code：

研究实施地点：

Countries of recruitment and research settings：

国家：	中国	省(直辖市)：	福建省	市(区县)：	福州市
Country：	China	Province：	Fujian	City：	Fuzhou
单位(医院)：	福建省肿瘤医院	单位级别：	三甲
Institution hospital：	Fujian Cancer Hospital	Level of the institution：	Tertiary A

国家：	中国	省(直辖市)：	安徽省	市(区县)：	合肥市
Country：	China	Province：	Anhui	City：	Hefei
单位(医院)：	中国科学技术大学附属第一医院（安徽省立医院）	单位级别：	三甲
Institution hospital：	The First Affiliated Hospital of USTC(Anhui Provincial Hospital)	Level of the institution：	Tertiary A

测量指标：

Outcomes：

指标中文名：	药代动力学	指标类型：	主要指标
Outcome：	Pharmacokinetics	Type：	Primary indicator
测量时间点：		测量方法：
Measure time point of outcome：		Measure method：

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

指标中文名：	心电图	指标类型：	次要指标
Outcome：	Electrocardiogram	Type：	Secondary indicator
测量时间点：		测量方法：
Measure time point of outcome：		Measure method：

指标中文名：	生命体征	指标类型：	次要指标
Outcome：	Vital signs	Type：	Secondary indicator
测量时间点：		测量方法：
Measure time point of outcome：		Measure method：

指标中文名：	药效动力学	指标类型：	次要指标
Outcome：	Pharmacodynamics	Type：	Secondary indicator
测量时间点：		测量方法：
Measure time point of outcome：		Measure method：

指标中文名：	最佳推荐剂量	指标类型：	主要指标
Outcome：	Optimal recommended dosage	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：
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：

尚未开始

Not yet recruiting

年龄范围：

Participant age：

最小 Min age	18	岁 years
最大 Max age		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：	无
Blinding：	None

是否共享原始数据： IPD sharing	否No
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）：	无
The way of sharing IPD”(include metadata and protocol, If use web-based public database, please provide the url)：	None
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：	病例报告表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：	CRF 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：	2025-05-16 17:04:50