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：	ChiCTR2300077119
最近更新日期： Date of Last Refreshed on：	2024-06-02 22:42:31
注册时间： Date of Registration：	2023-10-31 00:00:00
注册号状态：	预注册
Registration Status：	Prospective registration
注册题目：	YZJ-5053片在晚期实体瘤受试者中的I期研究
Public title：	A Phase 1 Study of YZJ-5053 Tablets in Participants with Advanced Solid Tumors
注册题目简写：
English Acronym：
研究课题的正式科学名称：	YZJ-5053片在晚期实体瘤受试者中的安全性、耐受性、药代动力学及初步有效性的I期研究
Scientific title：	A Phase 1 Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Efficacy of YZJ-5053 Tablets in Participants 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：	秦琴	研究负责人：	李进
Applicant：	Qin Qin	Study leader：	Jin Li
申请注册联系人电话： Applicant telephone：	+86 158 5057 4935	研究负责人电话： Study leader's telephone：	+86 137 6122 2111
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：	zhuce@haiyanpharma.com	研究负责人电子邮件： Study leader's E-mail：	lijin@csco.org.cn
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：	中国(上海)自由贸易试验区李冰路67弄8号	研究负责人通讯地址：	上海市浦东新区云台路1800号
Applicant address：	Building 8, Lane 67, Libing Road, China (Shanghai) Pilot Free Trade Zone	Study leader's address：	1800 Yuntai Road, Pudong New Area, Shanghai
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：	上海海雁医药科技有限公司
Applicant's institution：	Shanghai Haiyan Pharmaceutical Technology 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：	[2023]临审第(053)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（同济大学附属东方医院）医学伦理委员会
Name of the ethic committee：	Medical Ethics Committee of Shanghai East Hospital (East Hospital Affiliated to Tongji University)
伦理委员会批准日期： Date of approved by ethic committee：	2023-08-11 00:00:00
伦理委员会联系人：	鲍思蔚
Contact Name of the ethic committee：	Siwei Bao
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 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)：
Country：	Republic of China	Province：	Shanghai	City：
单位(医院)：	上海海雁医药科技有限公司	具体地址：	中国(上海)自由贸易试验区李冰路67弄8号
Institution hospital：	Shanghai Haiyan Pharmaceutical Technology Co., Ltd	Address：	Building 8, Lane 67, Libing Road, China (Shanghai) Pilot Free Trade Zone

经费或物资来源：

上海海雁医药科技有限公司

Source(s) of funding：

Shanghai Haiyan Pharmaceutical Technology Co., Ltd

研究疾病：

晚期实体瘤

Target disease：

Advanced solid tumor

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：

Ia期研究主要目的：确定最大耐受剂量（MTD）/II期临床研究推荐剂量（RP2D），评估YZJ-5053片单药治疗的安全性和耐受性； Ib期研究主要目的：确定RP2D，评估YZJ-5053片单药治疗的安全性和耐受性。

Objectives of Study：

stage 1a :To define the maximum tolerated dose (MTD) and/or a recommended phase 2 dose(RP2D). To evaluate the safety and tolerability of YZJ-5053 tables in participants with advanced solid tumors, stage 1b : To define the RP2D. To evaluate the safety and tolerability of YZJ-5053 tables in subjects 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

1.	Male or female subjects are >= 18 years of age on the day of signing the informed consent.
2.	Histologically or cytologically confirmed advanced or metastatic solid tumors who  have failed standard treatment, or are ineligible for the standard treatment, or have no standard treatment, or declined stansard treatment.
3.	Subjects must have at least one measurable target lesion in indication expansion phase (Part 2) as defined by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 criteria which has not received radiotherapy (or progressive disease after radiotherapy), or at least one evaluable lesion in dose escalation phase (Part 1) .
4.	Subjects with previously confirmed brain metastases were enrolled if they were clinically asymptomatic, in stable condition, and did not require steroid therapy for at least 4 weeks before the initiation of study treatment.
5.	Eastern Cooperative Oncology Group performance status (ECOG PS) of 0 or 1;
6.	Life expectancy at least 3 months;
7.	Adequate hematologic and organ function at screening and within 28 days prior to initiation of study treatment (without receiving any blood transfusion or hematopoietic stimulating factors within 2 weeks prior to screening),as evidenced by:
     ANC >= 1.5 x 10^9/L;
     Hemoglobin >=85 g/L;
     Platelets >= 75 x 10^9/L;
     AST or ALT <= 3 x ULN , or <= 5 x ULN if liver cancer or liver metastases are present.
     Total bilirubin < 1.5 x ULN , or < 3.0 x ULN for subjects with liver cancer or liver metastases or documented Gilbert’s syndrome (unconjugated hyperbilirubinemia);
     Serum creatinine (Scr) <1.5×ULN, or creatinine clearance (Ccr) > 50 mL/min according to Cockcroft-Gault equation;
     INR and APTT< 1.5 ULN;
8.	A woman of child-bearing potential (WOCBP) must have a negative serum pregnancy test within 72 hours prior to initiation of study treatment (serum pregnancy test is not required for females of nonchild-bearing potential who have undergone surgical sterilization, such as hysterectomy and/or bilateral oophorectomy, or those who have not experienced menses for 12 consecutive months and are judged to be postmenopausal based on factors such as age and castration therapy).
9.	Subjects must agree to use adequate contraceptive methods prior to initiation of study treatment, during the study, and for at least 6 months following the last dose of YZJ-5053 tablets, or for at least 4 months following the last dose of pembrolizumab, whichever is later.

排除标准：

1.处于妊娠期或哺乳期的女性受试者； 2.仅Ib期剂量扩展阶段：筛选前3年内有其他恶性肿瘤史，已治愈的宫颈原位癌、非黑色素瘤皮肤癌、前列腺原位癌或其他经过根治性治疗且至少3年无疾病迹象的肿瘤除外； 3.有控制不良的胸腔积液、心包积液或腹水，需要反复引流者（每月一次或更频繁）； 4.心脏功能受损或有临床显著心血管疾病； 5.有可能显著改变YZJ-5053吸收的胃肠道（gastrointestinal，GI）功能受损状况或疾病； 6.筛选时或给药前2周内出现活动性感染，需要抗生素系统性静脉给药治疗者； 7.筛选时HIV抗体阳性、乙肝表面抗原（HBsAg）阳性且乙肝病毒DNA≥2×10^3 IU/ml（相当于10^4拷贝/ml）、丙肝病毒抗体阳性患者； 8.在首次给药前3周内接受过化疗，前4周内接受过放疗、生物治疗、内分泌治疗、靶向治疗、免疫治疗等抗肿瘤治疗，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、小分子靶向药物以及有抗肿瘤适应症的中药为首次使用研究药物前 2 周内；在首次给药前 4 周内接受过其它未上市的临床研究药物或治疗； 9.在研究期间不能停用CYP3A和CPY2C8强抑制剂或诱导剂的受试者； 10.在首次给药前4周内接种过活疫苗或减毒活疫苗的受试者； 11.)既往接受过A2aR拮抗剂或双腺苷受体（A2aR/A2bR）拮抗剂的受试者； 12.在首次给药前，受试者在既往抗肿瘤治疗中发生的所有AEs尚未恢复到基线水平或≤1级（美国国家癌症研究所[National Cancer Institute，NCI]-CTCAE v5.0），但不包括以下情况：脱发（任何级别）、外周感觉神经病变（CTCAE≤2级）和其它无临床症状的单纯性实验室检查异常（CTCAE≤2级）的AE； 13.已知有自身免疫性甲状腺疾病如弥漫性毒性甲状腺肿（Graves病）或急性、亚急性甲状腺炎等病史的受试者；患有活动性或可能复发的自身免疫性疾病；除外：有自身免疫相关甲状腺功能减退的患者接受稳定剂量甲状腺激素替代治疗的；接受稳定的胰岛素治疗方案后得到控制的I型糖尿病患者； 14.在首次给药前4周内接受全身性皮质类固醇（＞10mg/天泼尼松等效药物）或其他全身性免疫抑制剂（包括但不限于泼尼松、地塞米松、环磷酰胺、硫唑嘌呤、甲氨蝶呤、沙利度胺和抗肿瘤坏死因子药物）的受试者，但不包括：局部、眼部、关节内、鼻内或吸入使用糖皮质激素；接受急性小剂量全身性免疫抑制药物（例如：单次使用地塞米松治疗恶心）的受试者，可与医学监查员讨论并且获得批准后入组；肾上腺或垂体功能不全等疾病替代类固醇剂量按泼尼松当量≤10 mg/天；盐酸皮质激素（例如氟氢可的松）治疗直立性低血压；短期（≤7天）使用类固醇进行预防或治疗非自身免疫性过敏性疾病；影像学增强检查前预防造影剂过敏一次性使用糖皮质激素的情况； 15.在开始研究治疗前4周内接受过重大手术的受试者或预期在研究期间需要接受重大手术的受试者； 16.存在可能导致不可接受的安全性风险或影响研究方案依从性的其他重度和/或控制不良的伴随疾病； 17.存在其他经研究者评估认为可能影响研究结果、对受试者参加试验产生干扰的状况、治疗或实验室检查异常。

Exclusion criteria：

1. Female subjects who are pregnant or breast-feeding. 2. History of malignancy within 3 years prior to screening, with the exception of the cancer under investigation in this study and curatively treated carcinoma in situ of the cervix, non-melanoma skin cancer, localized prostate cancer or any other tumor that has been treated curatively and with no evidence of disease for at least 3 years (for indication expansion phase [Part 2] only). 3. Presence of uncontrolled pleural effusion, pericardial effusion, or ascites that require recurrent drainage procedures (monthly or more frequently). 4. Impaired cardiac function or clinically significant cardiovascular disease. 5. Conditions or diseases that impair gastrointestinal (GI) function which may significantly alter the absorption of YZJ-5053 tables (e.g. ulcerative diseases, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, or small bowel resection). 6. Subjects with active infection requiring intravenous (IV) antibiotics at the time of screening or within 2 weeks prior to initiation of study treatment. 7. Subjects with positive HIV antibody, or positive hepatitis B surface antigen (HBsAg) with HBV DNA >= 2×10^3 IU/ml (equivalent to 10^4 copies/ml), or positive hepatitis C virus antibody at the time of screening; 8. Have received chemotherapy within 3 weeks, and radiotherapy, biological therapy, endocrine therapy, targeted therapy, immunotherapy or any other anti-tumor therapy within 4 weeks prior to initiation of study treatment, excluding the following: Within 6 weeks prior to the first use of the study drug, nitrosourea or mitomycin C; Oral administration of fluorouracil, small molecule targeted drugs, and traditional Chinese medicine with anti-tumor indications within 2 weeks prior to the first use of the study drug; Received other unlisted clinical research drugs or treatments within 4 weeks before the first administration; 9. Subject who could not discontinue use of strong inhibitors or strong inducers of CYP3A and CPY2C8 during the study period. 10. Subjects who have received a live vaccine or live attenuated vaccine within 4 weeks prior to initiation of study treatment. 11. Subjects who have previously received A2aR antagonists or A2aR/A2bR antagonists. 12. AEs from previous antitumor therapy have not recovered to baseline or to CTCAE Grade 1 prior to initiation of study treatment, excluding subjects with alopecia (any grade), peripheral sensory neuropathy (Grade <= 2), and any other toxicities of no clinical significance (Grade <= 2); 13. Subjects with a known history of autoimmune thyroid disease such as diffuse toxic goiter (Graves disease) , acute or subacute thyroiditis. Subjects with active autoimmune diseases or a known history of autoimmune diseases that potentially relapsing, exception: Subjects with autoimmune-related hypothyroidism requiring stable dose thyroxine replacement only are eligible; Subjects with type I diabetes mellitus controlled on a stable insulin regimen are eligible; 14. Subjects who have received systemic corticosteroids (> 10 mg/day prednisone equivalent) or other systemic immunosuppressants (including but not limited to prednisone, dexamethasone, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-TNF drugs) within 4 weeks prior to the initiation of study treatment, but excluded Locally, ocularly, intra-articularly, intranasally, or inhaled corticosteroids; Subjects receiving acute low-dose systemic immunosuppressive drugs (e.g., single dexamethasone for nausea) may be enrolled after discussion with and approval from medical monitor ; Alternative steroid doses for diseases such as adrenal or pituitary insufficiency are <= 10 mg/day in prednisone equivalents; Corticosteroids hydrochloride (eg fludrocortisone) for orthostatic hypotension; Short-term (<= 7 days) use of steroids for the prevention or treatment of non-autoimmune allergic diseases; Single ues of glucocorticoids before enhanced-imaging for prevention of contrast agent allergy; 15. Major surgical procedures, within 4 weeks prior to initiation of study treatment, or anticipation of need for major surgical procedure during the study period. 16. Other severe and/or uncontrolled concomitant medical conditions that could cause unacceptable safety risks or compromise compliance with the protocol. 17. Presence of other conditions, therapy, or laboratory abnormalities that, in the opinion of the investigator, might confound the results of the study and interfere with the subject’s participation.

研究实施时间：

Study execute time：

从 From 2023-07-01 00:00:00至 To 2027-10-31 00:00:00

征募观察对象时间：

Recruiting time：

从 From 2023-11-01 00:00:00 至 To 2027-10-31 00:00:00

干预措施：

Interventions：

组别：	Ia: 剂量递增	样本量：	47
Group：	Ia: Dose increasing	Sample size：	47
干预措施：	YJ-5053片，口服，QD。使用加速滴定及“i3+3”方法进行剂量递增。	干预措施代码：
Intervention：	YZJ-5053 tablets are administered orally QD. Accelerated titration and "i3+3" method were used for dose escalation.	Intervention code：

组别：	Ib: 剂量扩展	样本量：	110
Group：	Ib: Dose extension	Sample size：	110
干预措施：	YJ-5053片，口服，QD。	干预措施代码：
Intervention：	YZJ-5053 tablets are administered orally QD.	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)：
Country：	Republic of 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)：	山东省	市(区县)：
Country：	Republic of China	Province：	Shandong	City：
单位(医院)：	山东省肿瘤医院	单位级别：	三甲
Institution hospital：	Shandong Cancer Hospital	Level of the institution：	Tertiary A

国家：	中国	省(直辖市)：	浙江省	市(区县)：
Country：	Republic of China	Province：	Zhejiang	City：
单位(医院)：	浙江大学附属第二医院	单位级别：	三甲
Institution hospital：	The Second Affiliated Hospital Zhejiang University School of Medicine	Level of the institution：	Tertiary A

国家：	中国	省(直辖市)：	江西省	市(区县)：
Country：	Republic of China	Province：	Jiangxi	City：
单位(医院)：	南昌大学附属第一医院	单位级别：	三甲
Institution hospital：	The First Affiliated Hospital of Nanchang University	Level of the institution：	Tertiary A

测量指标：

Outcomes：

指标中文名：	安全性评价指标	指标类型：	主要指标
Outcome：	Safety evaluation 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：	PK特征	指标类型：	次要指标
Outcome：	PK characteristics	Type：	Secondary 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	指标类型：	次要指标
Outcome：	Efficacy evaluation 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：	代谢物	指标类型：	附加指标
Outcome：	Metabolites	Type：	Additional 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：	附加指标
Outcome：	Biomarker	Type：	Additional indicator
测量时间点：		测量方法：
Measure time point of outcome：		Measure method：

指标中文名：	MTD/RP2D 和剂量限制性毒性（DLT）	指标类型：	主要指标
Outcome：	MTD/RP2D and Dose Limited Toxicity (DLT)	Type：	Primary indicator
测量时间点：		测量方法：
Measure time point of outcome：		Measure method：

指标中文名：	RP2D	指标类型：	主要指标
Outcome：	RP2D	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：

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：	肿瘤组织	组织：
Sample Name：	Tumor tissue	Tissue：
人体标本去向	使用后保存	说明
Fate of sample：	Preservation 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）：

不适用

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

Not applicable

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	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）：	N/A
The way of sharing IPD”(include metadata and protocol, If use web-based public database, please provide the url)：	N/A
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：	EDC
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：	2023-10-31 14:46:52