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：	ChiCTR2300075191
最近更新日期： Date of Last Refreshed on：	2024-01-29 14:16:46
注册时间： Date of Registration：	2023-08-29 00:00:00
注册号状态：	预注册
Registration Status：	Prospective registration
注册题目：	评价BT02在晚期实体瘤患者中的安全性、耐受性、药代动力学特征、抗肿瘤疗效的I期开放性剂量探索研究
Public title：	A phase I open dose exploration study to evaluate the safety, tolerability, pharmacokinetic characteristics and anti-tumor efficacy of BT02 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BT02在晚期实体瘤患者中的安全性、耐受性、药代动力学特征、抗肿瘤疗效的I期开放性剂量探索研究
Scientific title：	A phase I open dose exploration study to evaluate the safety, tolerability, pharmacokinetic characteristics and anti-tumor efficacy of BT02 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：	罗放	研究负责人：	沈赞
Applicant：	Fang Luo	Study leader：	Zan Shen
申请注册联系人电话： Applicant telephone：	+86 133 7609 0864	研究负责人电话： Study leader's telephone：	+86 138 1606 7266
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：	fang.luo@biotroy.cn	研究负责人电子邮件： Study leader's E-mail：	sshenzzan@vip.sina.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：	上海市宝山区园丰路69号	研究负责人通讯地址：	上海市宜山路600号
Applicant address：	69 Yuanfeng Road, Baoshan District, Shanghai	Study leader's address：	600 Yishan Road, 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：	上海柏全生物科技有限公司
Applicant's institution：	Shanghai Biotroy Biotechnology CO,. Ltd.
研究负责人所在单位：	上海市第六人民医院
Affiliation of the Leader：	Shanghai Sixth People's 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：	2023-105	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：	上海市第六人民医院伦理委员会
Name of the ethic committee：	Ethics Committee of Shanghai Sixth People's Hospital
伦理委员会批准日期： Date of approved by ethic committee：	2023-08-03 00:00:00
伦理委员会联系人：	庞路阳
Contact Name of the ethic committee：	Luyang Pang
伦理委员会联系地址：	上海市宜山路600号
Contact Address of the ethic committee：	600 Yishan Road, Shanghai
伦理委员会联系人电话： Contact phone of the ethic committee：	+86 21 6436 9181	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：

上海市第六人民医院

Primary sponsor：

Shanghai Sixth People's Hospital

研究实施负责（组长）单位地址：

上海市宜山路600号

Primary sponsor's address：

600 Yishan Road, 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(区县)：
Country：	China	Province：	Shanghai	City：
单位(医院)：	上海市第六人民医院	具体地址：	上海市宜山路600号
Institution hospital：	Shanghai Sixth People's Hospital	Address：	600 Yishan Road, Shanghai

经费或物资来源：

自筹经费

Source(s) of funding：

self-financing

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：

探索性研究/预试验

Study phase：

0

研究设计：

单臂

Study design：

Single arm

研究目的：

主要目的： 1.评价BT02的安全性和耐受性； 2.确定BT02的最大耐受剂量（MTD）和/或推荐的II期剂量（RP2D）；次要目的： 1.描述BT02的药代动力学（PK）特征； 2.初步评价BT02的抗肿瘤疗效； 3.评估BT02的免疫原性；探索性目的：； 1.探索BT02的药效动力学（PD）特征； 2.评估潜在的预测生物标记物，包括： 1）组织IT1,PD-L1表达； 2）外周血IT1的受体占有率，CD8+T细胞比例； 3.评估药物暴露量和毒性以及药效之间的关系。

Objectives of Study：

Main purpose: 1. Evaluate the safety and tolerability of BT02; 2. Determine the maximum tolerable dose (MTD) of BT02 and/or the recommended Phase II dose (RP2D); Secondary purpose: 1. Describe the pharmacokinetic (PK) characteristics of BT02; 2. Preliminary evaluation of the anti-tumor efficacy of BT02; 3. Evaluate the immunogenicity of BT02; Exploratory purposes:; 1. Explore the pharmacokinetic (PD) characteristics of BT02; 2. Evaluate potential predictive biomarkers, including: 1) Organize the expression of IT1 and PD-L1; 2) The occupancy rate of peripheral blood IT1 receptors and the proportion of CD8+T cells; 3. Evaluate the relationship between drug exposure, toxicity, and efficacy.

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. Voluntarily participate in clinical research; Fully understand and be aware of this study and sign the ICF; Willing to follow and capable of completing all testing procedures;
2. Age:>=18 years old (subjects with osteosarcoma and soft tissue sarcoma>=14 years old), both male and female;
3. The enrolled subjects must have advanced or metastatic solid tumors confirmed by histology or cytology (non resectable), standard treatment fails, there is no standard treatment, or the subjects refuse standard treatment;
4. Subjects with ECOG score of 0 or 1 in physical fitness status;
5. According to RECIST v1.1 (solid tumors), the subject has at least one measurable or evaluable lesion that has not been locally treated in the past [bone only or central nervous system (CNS) only metastases are not accepted as measurable lesions];
6. An exected survival period of at least 3 months, with the ability to follow up on safety and efficacy data;
7. If the subject has received anti-tumor treatment in the past, they should be enrolled only after the toxic reactions of previous treatments have returned to baseline levels (except for residual hair loss effects) or the CTCAE v5.0 score is<=1 level;
8. Adequate organ and bone marrow function, without severe hematopoietic dysfunction, heart, lung, liver, kidney dysfunction, and immune deficiency (no medical support such as blood transfusion, granulocyte colony-stimulating factor (G-CSF), or other medical support received within 14 days prior to the use of the study drug):
1) ANC>=1.5 × 10 ^ 9/L;
2) Platelets>=100 × 10 ^ 9/L; Phase Ib: For HCC subjects, platelet count ≥ 80 × 10 ^ 9/L;
3) Hemoglobin>=9 g/dL;
4) Serum creatinine<=1.5 times the upper limit of normal value (ULN), creatinine clearance rate>60 mL/min (estimated based on Cockcroft Gault formula) can be enrolled (note: creatinine clearance rate needs to be confirmed only when serum creatinine is 1.5 times higher than the upper limit of the reference range of normal values);
5) Serum total bilirubin<=1.5 times ULN;
6) Aspartate aminotransferase (AST) and alanine aminotransferase (ALT)<=2.5 times ULN; For subjects with liver cancer or liver metastasis, AST and ALT<=5 times ULN;
7) International standardized ratio (INR) or plasma prothrombin time (PT)<=1.5 times ULN.
9. Female or male participants of childbearing age and their partners should agree to take effective contraceptive measures within 6 months from signing the ICF until the last dose of the study drug is used.

排除标准：

1.已知患有原发性CNS肿瘤，或脑膜转移受试者，或不稳定性CNS转移受试者（在开始研究治疗前4周内有症状、需要激素治疗，或没有影像学证据表明病灶稳定超过4周）； 2.患有活动性、或曾患过且有可能复发的自身免疫性疾病（如：全身性红斑狼疮、类风湿性关节炎、炎症性肠病、自身免疫性甲状腺疾病、血管炎、银屑病，等）或风险（如接受过器官移植需要接受免疫抑制治疗）的受试者。但允许患以下疾病的受试者进一步入组筛选：I型糖尿病、只需接受激素替代治疗的甲状腺功能减退症、无需进行全身治疗的皮肤疾病（如白癜风、银屑病或脱发）； 3.在研究药物给药前14天内因某种状况需接受糖皮质激素（强的松 > 10 mg/天或等价剂量的其它同类药物）或其他免疫抑制剂治疗的受试者；注意：在无活动性自身免疫疾病时，允许使用强的松或同等药物剂量 <= 10 mg/天的肾上腺药物替代给药；允许受试者使用局部、眼部、关节腔内、鼻内和吸入型糖皮质激素治疗（全身吸收程度极低）；允许短期（<= 7天）使用糖皮质激素进行预防治疗（例如造影剂过敏）或用于治疗非自身免疫疾病（例如，接触性过敏原所致迟发型超敏反应）； 4.开始研究治疗前14天接受过全身性抗肿瘤治疗，包括化疗、免疫治疗、生物治疗（肿瘤疫苗、细胞因子、或控制癌症的生长因子）等； 5.开始研究治疗前28天内进行过重大手术，或根治性放射治疗，或前14天内进行过姑息性放射治疗，或56天内使用过放射药剂（锶、钐等）； 6.开始研究治疗前7天内接受过抗肿瘤适应症的中草药或中成药治疗； 7.曾患间质性肺病、化学性肺炎、过敏性肺炎、结缔组织病肺炎、肺纤维化、急性肺部疾病等（由放疗诱发的局部间质性肺炎除外），或未控制的系统性疾病，包括糖尿病、高血压等； 8.已知有人类免疫缺陷病毒（HIV）病毒感染病史的受试者； 9.慢性乙型肝炎活动期或活动性丙型肝炎受试者。筛选期乙肝表面抗原（HBsAg）或丙型肝炎病毒（HCV）抗体阳性的受试者，必须在进一步通过乙型肝炎病毒（HBV）DNA滴度检测（不得高于1000拷贝[cps]/mL或200 IU/mL）和HCV RNA检测（超过测定法的检测下限），在排除了需接受治疗的活动性乙型肝炎或丙型肝炎感染之后，方可入组试验。乙肝病毒携带者、经药物治疗后稳定的乙肝（DNA滴度不得高于1000拷贝[cps]/mL或200 IU/mL）和已治愈的丙肝受试者可以入组； 10. 活动性肺结核病受试者； 11. 开始研究治疗前2周内出现任何需要系统性全身治疗的活动性感染； 12. 曾接受过实体器官移植者； 13. 曾接受免疫治疗出现irAE等级>= 3级者； 14. 已知对单抗有严重过敏反应者（CTCAE v5.0分级大于3级），及有不受控制的过敏性哮喘病史的受试者； 15. 妊娠期或哺乳期女性；不愿采取适当避孕措施的男性或女性；育龄期女性须于筛选期接受妊娠试验； 16. 已知有酗酒或药物滥用史者； 17. 患有重大心血管疾病者（如：充血性心力衰竭、不稳定型心绞痛、房颤、心律失常，等）：入选前6个月内发生急性心肌梗死、不稳定心绞痛、中风、或短暂性缺血性发作等疾病史，美国纽约心脏病学会（NYHA）分级为2级以上（含2级）的充血性心力衰竭；左心室射血分数（LVEF） < 50%；及患有以下心脏疾病的受试者： a) 筛选期心电图（ECG）QTc间期 > 480 msec（QTc间期以Fridericia公式计算）； b) 右束支传导阻滞 + 左前半支传导阻滞或完全性左束支阻滞； c) 先天性长QT综合征的受试者； d) 患有室性快速性心律失常或具有该病史的受试者； e) 具有明显临床意义的心动过缓（< 50 次/分）； f) 使用心脏起搏器的受试者； g) 其它具有明显临床意义的心脏病受试者； 18. 开始研究治疗前4周内存在不能控制的胸腔积液、心包积液，或需要反复引流的腹水（注意：允许存在仅可通过影像学检查发现的少量腹水）； 19. 有精神病史者； 20. 无行为能力者或限制行为能力者； 21. 经研究者判断，受试者基础病情可能会增加其接受研究药物治疗的风险，或是对于出现的毒性反应及AE的解释造成混淆的； 22. 其它研究者认为不适合参加本研究的情况。

Exclusion criteria：

1. Subjects with known primary CNS tumors, meningeal metastases, or unstable CNS metastases (with symptoms within 4 weeks prior to the start of study treatment, requiring hormone therapy, or no imaging evidence indicating lesion stability for more than 4 weeks); 2. Participants with active or potentially recurrent autoimmune diseases (such as systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, autoimmune thyroid disease, vasculitis, psoriasis, etc.) or at risk (such as immunosuppressive therapy required for organ transplantation). However, subjects suffering from the following diseases are allowed to be further included in the group for screening: type I diabetes, hypothyroidism only requiring hormone replacement treatment, and skin diseases (such as vitiligo, psoriasis, or alopecia) that do not require systemic treatment; 3. Subjects who require treatment with glucocorticoids (prednisone>10 mg/day or equivalent doses of other similar drugs) or other immunosuppressants due to certain conditions within 14 days prior to drug administration in the study; Attention: In the absence of active autoimmune diseases, it is allowed to use prednisone or equivalent adrenal drugs with a dose of<=10 mg/day as a substitute for administration; Allow subjects to use local, ocular, intra-articular, intranasal, and inhaled corticosteroids for treatment (with extremely low systemic absorption); Allow short-term (<=7 days) use of glucocorticoids for preventive treatment (such as contrast agent allergies) or for the treatment of non autoimmune diseases (such as delayed hypersensitivity reactions caused by contact allergens); 4. Have received systemic anti-tumor therapy, including chemotherapy, immunotherapy, and biological therapy (tumor vaccines, cytokines, or growth factors that control cancer) 14 days prior to starting the study; 5. Major surgery, curative radiation therapy, palliative radiation therapy, or use of radiation agents (strontium, samarium, etc.) within 28 days prior to the start of research treatment; 6. Have received Chinese herbal medicine or traditional Chinese patent medicines and simple preparations with anti-tumor indications within 7 days before starting the research treatment; 7. Have ever suffered from interstitial lung disease, chemical pneumonia, allergic pneumonia, connective tissue disease pneumonia, pulmonary fibrosis, acute lung disease, etc. (except for local interstitial pneumonia induced by radiotherapy), or uncontrolled systemic diseases, including diabetes, hypertension, etc; 8. Subjects with a known history of human immunodeficiency virus (HIV) infection; 9. Subjects with active chronic hepatitis B or active hepatitis C. Subjects with positive hepatitis B B surface antigen (HBsAg) or hepatitis C virus (HCV) antibody in screening period must further pass the hepatitis B virus (HBV) DNA titer test (not higher than 1000 copies [cps]/mL or 200 IU/mL) and HCV RNA test (exceeding the detection limit of the test method). After excluding active hepatitis B or hepatitis C infection requiring treatment, they can be included in the test. Hepatitis B virus carriers, hepatitis B patients stabilized after drug treatment (DNA titer shall not be higher than 1000 copies [cps]/mL or 200 IU/mL) and cured hepatitis C patients can be included in the group; 10. Subjects with active pulmonary tuberculosis; 11. Any active infection requiring systemic systemic treatment within 2 weeks prior to the start of the study; 12. Individuals who have received solid organ transplants; 13. Individuals who have received immunotherapy and experienced irAE levels>=3; 14. Subjects with known severe allergic reactions to monoclonal antibodies (CTCAE v5.0 grade greater than 3) and a history of uncontrolled allergic asthma; 15. Pregnant or lactating women; Men or women who are unwilling to take appropriate contraceptive measures; Women of childbearing age must undergo pregnancy trials during the screening period; 16. Individuals with a known history of alcohol or drug abuse; 17. Individuals with major cardiovascular diseases (such as congestive heart failure, unstable angina, atrial fibrillation, arrhythmia, etc.): those with a history of acute myocardial infarction, unstable angina, stroke, or transient ischemic attack within the 6 months prior to enrollment, and those with congestive heart failure classified by the New York Heart Association (NYHA) as grade 2 or above (including grade 2); Left ventricular ejection fraction (LVEF)<50%; And subjects with the following heart diseases: a) Screening period electrocardiogram (ECG) QTc interval>480 msec (QTc interval calculated using Fridericia formula); b) Right bundle branch block+left anterior half branch block or complete left bundle branch block; c) Subjects with congenital long QT syndrome; d) Subjects with ventricular tachycardia or a history of the disease; e) Bradycardia with significant clinical significance (<50 beats/minute); f) Subjects using pacemakers; g) Other heart disease subjects with significant clinical significance; 18. Starting the study, there may be uncontrollable pleural effusion, pericardial effusion, or ascites that require repeated drainage within 4 weeks prior to treatment (note: only a small amount of ascites that can be detected through imaging examination is allowed); 19. Individuals with a history of mental illness; 20. Individuals without or with limited capacity for behavior; 21. According to the judgment of the researchers, the basic condition of the subjects may increase their risk of receiving treatment with the investigational drug, or cause confusion in the interpretation of toxic reactions and AEs that may occur; 22. Other researchers deemed it unsuitable to participate in this study.

研究实施时间：

Study execute time：

从 From 2023-06-01 00:00:00至 To 2024-12-31 00:00:00

征募观察对象时间：

Recruiting time：

从 From 2023-09-01 00:00:00 至 To 2024-12-31 00:00:00

干预措施：

Interventions：

组别：	试验组	样本量：	21
Group：	Experimental group	Sample size：	21
干预措施：	用约250 mL无菌生理盐水（0.9%氯化钠溶液），稀释待给药的总剂量（根据受试者体重及剂量组计算得出），给患者静脉输注给药	干预措施代码：
Intervention：	About 250 mL sterile saline (0.9% sodium chloride solution) was used to dilute the total dose to be administered (calculated according to the subject's body weight and dose group), and the patient was given intravenous infusion	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)：
Country：	China	Province：	Shanghai	City：
单位(医院)：	上海市第六人民医院	单位级别：	三甲
Institution hospital：	Shanghai Sixth People's Hospital	Level of the institution：	Tertiary A

测量指标：

Outcomes：

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

指标中文名：	耐受性	指标类型：	主要指标
Outcome：	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：	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：	推荐的II期剂量	指标类型：	主要指标
Outcome：	Recommended phase II 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：	药代动力学（PK）特征	指标类型：	次要指标
Outcome：	Pharmacokinetic (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：	抗肿瘤疗效	指标类型：	次要指标
Outcome：	Antitumor effect	Type：	Secondary indicator
测量时间点：		测量方法：
Measure time point of outcome：		Measure method：

指标中文名：	免疫原性	指标类型：	次要指标
Outcome：	Immunogenicity	Type：	Secondary 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	14	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：
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）：	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：	数据通过EDC系统记录
Data collection and Management (A standard data collection and management system include a CRF and an electronic data capture：	Record data through the EDC system
数据与安全监察委员会： Data and Safety Monitoring Committee：	暂未确定/Not yet
注册人： Name of Registration：	2023-08-29 11:12:12