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：	ChiCTR2200066256
最近更新日期： Date of Last Refreshed on：	2023-07-02 22:39:16
注册时间： Date of Registration：	2022-11-29 00:00:00
注册号状态：	预注册
Registration Status：	Prospective registration
注册题目：	SYS6002剂量递增、PK扩展及队列扩展研究的Ⅰ期临床试验
Public title：	Phase I, Dose Escalation, PK Expansion and Cohort Expansion study of SYS6002 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SYS6002在晚期实体瘤患者中的安全性、耐受性、药代动力学特征和初步疗效的开放、单臂、多中心的Ⅰ期临床试验
Scientific title：	An Open-label, Single-arm, Multi-center, Phase I Clinical Study to Evaluate the Safety, Tolerability, Pharmacokinetic Profile and Preliminary Efficacy of SYS6002 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：	张利琼	研究负责人：	叶定伟、张剑
Applicant：	Zhang Liqiong	Study leader：	Ye Dingwei, Zhang Jian
申请注册联系人电话： Applicant telephone：	+86 0311-67808678	研究负责人电话： Study leader's telephone：	+86 18221299571, +86 18017312991
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：	zhangliqiong@cspc.cn	研究负责人电子邮件： Study leader's E-mail：	fuscc2012@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：	河北省石家庄市黄河大道226号	研究负责人通讯地址：	上海市徐汇区东安路270号
Applicant address：	226 Huanghe Avenue, High tech Zone, Shijiazhuang, Hebei	Study leader's address：	270 Dong'an Road, Xuhui District, Shanghai
申请注册联系人邮政编码： Applicant postcode：	050000	研究负责人邮政编码： Study leader's postcode：	200032
申请人所在单位：	石药集团中奇制药技术（石家庄）有限公司
Applicant's institution：	CSPC Zhongqi Pharmaceutical Technology (Shijiazhuang) 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：	2210262-25	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伦理委员会
Name of the ethic committee：	Ethics Committee on clinical trials, Fudan University Shanghai Cancer Center
伦理委员会批准日期： Date of approved by ethic committee：	2022-10-10 00:00:00
伦理委员会联系人：	陆琴、张玮静
Contact Name of the ethic committee：	Lu Qin, Zhang Weijing
伦理委员会联系地址：	上海市徐汇区东安路270号
Contact Address of the ethic committee：	270 Dong'an Road, Xuhui District, Shanghai
伦理委员会联系人电话： Contact phone of the ethic committee：	+86 21 34778299	伦理委员会联系人邮箱： Contact email of the ethic committee：	Andwater@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：

上海市徐汇区东安路270号

Primary sponsor's address：

270 Dong'an Road, Xuhui 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)：	河北	市(区县)：	石家庄
Country：	China	Province：	Hebei	City：	Shijiazhuang
单位(医院)：	石药集团巨石生物制药有限公司	具体地址：	河北省石家庄市黄河大道226号
Institution hospital：	CSPC Megalith Biopharmaceutical Co., Ltd..	Address：	226 Huanghe Avenue, High Tech Zone, Shijiazhuang, Hebei

经费或物资来源：

石药集团巨石生物制药有限公司

Source(s) of funding：

CSPC Megalith Biopharmaceutical 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：

评价SYS6002在晚期实体瘤患者中的安全性和耐受性，确定SYS6002的最大耐受剂量（MTD）（如有）及II期临床研究推荐剂量（RP2D）。

Objectives of Study：

To evaluate the safety and tolerability of SYS6002 in patients with advanced solid tumors and determine the Maximum Tolerated Dose (MTD) (if any) of SYS6002 and the Recommended Phase II Dose (RP2D).

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. Age >= 18 years old, regardless of gender;
2. Patients with advanced solid tumors confirmed by pathology who have failed or are intolerant to standard treatment, have no standard treatment, or refuse standard treatment;
3. According to the Solid Tumor Efficacy Evaluation Standard (RECIST) v1.1, at least one measurable lesion confirmed by CT or MRI;
4. The Eastern Oncology Collaborative Group (ECOG) physical fitness score is 0-1;
5. Expected survival time ≥ 3 months;
6. Within 7 days before treatment, the main organ function meets the following criteria: blood routine (no blood transfusion, EPO, G-CSF, or other medical support treatment received within 14 days before the study drug administration): absolute neutrophil count >= 1.5 * 10^9/L, platelet >= 100 * 10^9/L, hemoglobin (Hb) >= 90g/L or >= 5.6 mmol/L; Renal function: serum creatinine clearance rate, dose increase, PK expansion, and queue expansion stage subjects: >= 30 mL/min, calculated based on Cockcroft Goult formula or 24-hour urine test; Subjects with severe renal insufficiency in the stage of increased dose and PK expansion of urothelial carcinoma: >= 15 mL/min and<30 mL/min, calculated based on the Cockcroft Gault formula or 24-hour urine test; Liver function: Total bilirubin <= 1.5 * ULN, Gilbert syndrome can be relaxed by <= 3 * ULN, ALT, and AST <= 2.5 * ULN, if there is liver metastasis, <= 5 * ULN; ALT and AST <= 1.5 for subjects with renal insufficiency at dose increasing and expanding stages of urothelium carcinoma × ULN; Coagulation function: activated partial thrombin time <= 1.5 * ULN, international standardized ratio <= 1.5 * ULN;
7. Subjects with Fertility should use contraceptives (such as Intrauterine device [IUD], contraceptives or condoms) during the study period and within 6 months after the end of the study, and men should avoid sperm donation; Women of childbearing age had negative serum Pregnancy test within 7 days before the study was included, and must be non-lactating women;
8. Volunteer to participate in this clinical study, understand the research procedures, and be able to sign an informed consent form in writing.

排除标准：

1. 活动性中枢神经系统转移和/或软脑膜转移。活动性中枢神经系统转移包括有症状（既往或新发）和无症状（既往或新发）但需要治疗的中枢神经系统转移者。如果中枢神经系统转移仅限于幕上和/或小脑（即无中脑、脑桥、延髓或脊髓转移）并已经接受过局部治疗，并且神经系统症状能够在首次使用试验药物前至少2周达到稳定，且不需要接受激素治疗或者接受≤ 10 mg/天的泼尼松（或等价激素），则可以参加研究； 2. 根据NCI-CTCAE v5.0，既往抗肿瘤治疗引起的不良事件未恢复至 1级（脱发除外；根据研究者的判断，经与申办者协商后，部分可耐受的慢性2级毒性可除外）； 3. 可能妨碍患者参加研究的任何严重和/或未经控制的并存疾病：（1）首次使用试验药物前6个月内有严重的心血管疾病史，包括但不限于： 1）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、III度房室传导阻滞等；Fridericia法校正QT间期> 480 ms（Fridericia公式：QTcF = QT/RR0.33，RR = 60/心率）； 2）有心肌梗塞、不稳定性心绞痛、血管成形术、冠状动脉架桥外科病史； 3）纽约心脏病学会(NYHA)分级为III级及以上心力衰竭；筛选期检查显示左室射血分数(LVEF) ＜ 50%。（2）其他具有临床意义的疾病： 1）HbA1C ≥ 8%； 2）有活动性角膜炎和角膜溃疡者； 3）首次使用试验药物前存在2级神经病变； 4）首次使用试验药物前4周内存在重度感染，包括但不限于需住院治疗的菌血症、重症肺炎等；首次使用试验药物前2周内存在需使用系统抗生素、抗病毒或抗真菌治疗的CTCAE v5.0 ≥ 2级的活动性感染； 5）活动性HBV或HCV感染（HBV-DNA ≥ 2000 IU/mL，HCV抗体阳性且HCV RNA高于分析方法检测下限）； 6）有免疫缺陷病史（包括HIV检测阳性，其他获得性、先天性免疫缺陷疾病）或器官移植史； 7）首次使用试验药物前5年内患有其他任何恶性肿瘤，除外已手术根治的皮肤基底细胞癌和宫颈原位癌等。 4. 既往治疗：（1）研究首次使用试验药物前4周内接受过其它未上市的临床试验药物或治疗；（2）最近一次抗肿瘤治疗距离首次使用试验药物时间满足以下时间间隔：首次使用试验药物前4周内接受过化疗、放疗、靶向治疗、免疫治疗和其他临床试验药物等抗肿瘤治疗；首次使用试验药物前2周内接受过口服氟尿嘧啶类、小分子靶向药物和有抗肿瘤适应症的中药；首次使用试验药物前2周内接受姑息性放疗或局部治疗；（3）在研究首次使用试验药物前4周内接受过的重大手术。 5. 首次使用试验药物前14天内接受过CYP3A4强抑制剂或强诱导剂、或P-gp抑制剂或诱导剂； 6. 已知对SYS6002产品的任何组分（抗体偶联毒素、抗体、毒素MMAE等）过敏，或对人源化单克隆抗体产品过敏； 7. 根据研究者的判断，有严重危害患者安全、或影响患者完成本研究的伴随疾病（如控制不佳的高血压和精神病等）或其他任何情况。

Exclusion criteria：

1. With active central nervous system (CNS) metastasis and/or leptomeningeal metastasis. The participants with active CNS metastasis include participants with symptomatic (previous or new onset) and asymptomatic (previous or new onset) CNS metastasis requiring treatment. If central nervous system metastasis is limited to the supratentorial ventricles and/or cerebellum (i.e., no metastasis to the midbrain, pons, medulla or spinal cord), local treatment is received, the neurological symptoms have become stable for at least 2 weeks before the first dose of the investigational drug and no hormonal therapy or prednisone (or equivalent) of <= 10 mg/day is required, the participants can be enrolled in the study.
2. The adverse events due to previous anti-tumor treatments without recovering toGrade 1 (except for alopecia; some tolerable chronic toxicities of Grade 2 may be excluded after consultation with the sponsor, as judged by the investigator) according to NCI-CTCAE v5.0;
3. Any serious and/or uncontrolled concurrent illness that may interfere with the study participation by the patients:
(1) Participants with a history of severe cardiovascular disease within 6 months before the first dose of the investigational drug, including but not limited to:
1) Severe cardiac rhythm or conduction abnormalities, such as ventricular arrhythmia and third-degree atrioventricular block requiring clinical intervention; corrected QT interval > 480 ms by Fridericia method (Fridericia formula: QTcF = QT/RR0.33, RR = 60/heart rate);
2) With history of myocardial infarction, unstable angina pectoris, angioplasty and coronary artery bypass surgery;
3) Grade III and above heart failure by New York Heart Association (NYHA) classification; in the tests and examinations during the screening period, left ventricular ejection fraction (LVEF) < 50%.
(2) Other clinically significant diseases:
1) HbA1C >= 8%;
2) With active keratitis and corneal ulcer;
3) With >= Grade 2 neuropathy before the first dose of the investigational drug;
4) Severe infection within 4 weeks before the first use of the investigational drug, including but not limited to bacteremia and severe pneumonia requiring hospitalization; active infection of >= Grade 2 of CTCAE v5.0 requiring systemic antibiotics, antiviral or antifungal therapy within 2 weeks before the first dose of the investigational drug;
5) Active HBV or HCV infection HBV DNA >= 2000 IU/mL, HCV antibody positive and HCV RNA higher than the lower LOD of the analytical method);
6) Those with a history of immunodeficiency (HIV-positive, acquired or congenital immunodeficiency, etc.), or organ transplantation;
7) Any other malignant tumor within 5 years before the first dose of the investigational drug, except for cured skin basal cell carcinoma and cervical carcinoma in situ after surgery.
4. Prior therapy:
(1) Have received other unmarketed clinical investigational drugs or treatments within 4 weeks before the first dose of the investigational drug in the study;
(2) The time interval between the latest anti-tumor treatment and the first dose of the investigational drug meets the following requirements: Have received anti-tumor treatments such as chemotherapy, radiotherapy, targeted therapy, immunotherapy and other clinical investigational drugs within 4 weeks before the first dose of the investigational drug; have received oral fluoropyrimidines, small molecule targeted drugs and traditional Chinese medicines with anti-tumor indications within 2 weeks before the first dose of the investigational drug; have received palliative radiotherapy or local therapy within 2 weeks before the first dose of investigational drug;
(3) Have received major surgery within 4 weeks before the first dose of the investigational drug in the study.
5. Have received strong inhibitor of CYP3A4 or inducer, or P-gp inhibitor or inducer within 14 days before the first dose of the investigational drug;
6. Hypersensitive to any components of SYS6002 product (antibody-toxin conjugate, antibody and toxin MMAE, etc.), or Hypersensitive to humanized monoclonal antibody products;
7. Concomitant diseases (such as poorly controlled hypertension and psychosis) or any other conditions that seriously endanger the safety of the patient or affect the completion of the study by the patient according to the investigator's judgment.

研究实施时间：

Study execute time：

从 From 2022-12-01 00:00:00至 To 2025-12-31 00:00:00

征募观察对象时间：

Recruiting time：

从 From 2022-12-01 00:00:00 至 To 2025-12-31 00:00:00

干预措施：

Interventions：

组别：	试验组	样本量：	366
Group：	Test group	Sample size：	366
干预措施：	SYS6002	干预措施代码：
Intervention：	SYS6002	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(区县)：	徐汇
Country：	China	Province：	Shanghai	City：	Xuhui
单位(医院)：	复旦大学附属肿瘤医院	单位级别：	三甲
Institution hospital：	Fudan University Shanghai Cancer Center	Level of the institution：	Tertiary A

测量指标：

Outcomes：

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

指标中文名：	II期推荐剂量	指标类型：	主要指标
Outcome：	Recommended Phase II Dose, RP2D	Type：	Primary indicator
测量时间点：		测量方法：
Measure time point of outcome：		Measure method：

指标中文名：	不良事件（AE）	指标类型：	主要指标
Outcome：	Adverse Event (AE)	Type：	Primary indicator
测量时间点：		测量方法：
Measure time point of outcome：		Measure method：

指标中文名：	严重不良事件（SAE）	指标类型：	主要指标
Outcome：	Serious Adverse Event (SAE)	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）：

非随机

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

Not Randomization

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）：	不
The way of sharing IPD”(include metadata and protocol, If use web-based public database, please provide the url)：	NO
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：	不
Data collection and Management (A standard data collection and management system include a CRF and an electronic data capture：	NO
数据与安全监察委员会： Data and Safety Monitoring Committee：	无/No
注册人： Name of Registration：	2022-11-29 16:53:11