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：	ChiCTR2300077953
最近更新日期： Date of Last Refreshed on：	2024-07-07 15:19:35
注册时间： Date of Registration：	2023-11-24 00:00:00
注册号状态：	预注册
Registration Status：	Prospective registration
注册题目：	BM201 注射液联合放射治疗及 PD-1 单抗在晚期实体瘤患者中的安全性、耐受性和初步疗效探索的临床研究
Public title：	Clinical study on the safety, tolerability, and preliminary efficacy of BM201 injection combined with radiation therapy and PD-1 monoclonal antibody 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：	BM201 注射液联合放射治疗及 PD-1 单抗在晚期实体瘤患者中的安全性、耐受性和初步疗效探索的临床研究
Scientific title：	Clinical study on the safety, tolerability, and preliminary efficacy of BM201 injection combined with radiation therapy and PD-1 monoclonal antibody 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：	李茹恬	研究负责人：	刘宝瑞
Applicant：	Rutian Li	Study leader：	Baorui Liu
申请注册联系人电话： Applicant telephone：	+86 138 1386 3961	研究负责人电话： Study leader's telephone：	+86 137 7062 1908
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：	Lirutian@njglyy.com	研究负责人电子邮件： Study leader's E-mail：	baoruiliu@nju.edu.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：	中国江苏省南京市中山南路321号	研究负责人通讯地址：	中国江苏省南京市中山南路321号
Applicant address：	321 Zhongshan Road South, Nanjing, Jiangsu, China	Study leader's address：	321 Zhongshan Road South, Nanjing, Jiangsu, 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：	南京大学医学院附属南京鼓楼医院
Applicant's institution：	Nanjing Drum Towel Hospital The Affiliated Hospital of Nanjing University Medical School
研究负责人所在单位：	南京大学医学院附属南京鼓楼医院
Affiliation of the Leader：	Nanjing Drum Towel Hospital The Affiliated Hospital of Nanjing University Medical School

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：	2023-364-02	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：	南京大学医学院附属南京鼓楼医院医学伦理委员会
Name of the ethic committee：	Medical Ethics Committee of Nanjing Drum Towel Hospital The Affiliated Hospital of Nanjing University Medical School
伦理委员会批准日期： Date of approved by ethic committee：	2023-10-10 00:00:00
伦理委员会联系人：	姜佩佩
Contact Name of the ethic committee：	Peipei Jiang
伦理委员会联系地址：	中国江苏省南京市中山南路321号
Contact Address of the ethic committee：	321 Zhongshan Road South, Nanjing, Jiangsu, China
伦理委员会联系人电话： Contact phone of the ethic committee：	+86 25 6818 2923	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：

南京大学医学院附属南京鼓楼医院

Primary sponsor：

Nanjing Drum Towel Hospital The Affiliated Hospital of Nanjing University Medical School

研究实施负责（组长）单位地址：

中国江苏省南京市中山南路321号

Primary sponsor's address：

321 Zhongshan Road South, Nanjing, Jiangsu, China

试验主办单位(项目批准或申办者)：

Secondary sponsor：

国家：	中国	省(直辖市)：	江苏省	市(区县)：	南京市
Country：	China	Province：	Jiangsu	City：	Nanjing
单位(医院)：	南京大学医学院附属南京鼓楼医院	具体地址：	中国江苏省南京市中山南路321号
Institution hospital：	Nanjing Drum Towel Hospital The Affiliated Hospital of Nanjing University Medical School	Address：	321 Zhongshan Road South, Nanjing, Jiangsu, China

经费或物资来源：

苏州百迈生物医药有限公司

Source(s) of funding：

InnoBM Pharmaceuticals

研究疾病：

肿瘤

Target disease：

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：

1.主要目的：评价 BM201 联合放射治疗及信迪利单抗的安全性和耐受性，确定剂量限制性毒性（DLT）、最大耐受剂量（MTD）和推荐的联合用药的剂量； 2.次要目的：评估 BM201 联合放射治疗及信迪利单抗的初步抗肿瘤疗效； 3.探索目的：探索相关生物标志物与疗效或安全性的相关性。

Objectives of Study：

1. Main purpose: To evaluate the safety and tolerability of BM201 combined with radiation therapy and sintilimab, determine dose limited toxicity (DLT), maximum tolerated dose (MTD), and recommended dosage for the combination therapy; 2. Secondary purpose: To evaluate the preliminary anti-tumor efficacy of BM201 combined with radiation therapy and sintilimab; 3. Exploratory Purpose: To explore the correlation between relevant biomarkers and efficacy or safety.

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. In screening period, aged 18-75 years old;
2. The Eastern Oncology Collaborative Group (ECOG)  score of 0-2;
3. Expected survival time of more than 3 months;
4. Solid tumor patients confirmed by histology or cytology as unresectable locally advanced or metastatic, with standard treatment failure or inability to receive standard treatment;
Cohort 1: Advanced melanoma;
Cohort 2: Advanced soft tissue sarcoma;
Cohort 3: Other advanced solid tumors except for Cohort 1 and 2;
5. According to the relevant evaluation criteria for tumor immunotherapy (irRECIST), patients must have at least one measurable tumor lesion, and the baseline lesion volume must be >= 6.00 × 10^3 mm3) and the lesion is suitable for intratumoral injection;
6. Women of childbearing age have negative serum pregnancy test results within 7 days before the first dose/radiation therapy, and are willing to use effective contraception methods during the study period and within 3 months after the last dose; And it must be non lactating. Male patients with female partners of childbearing age must agree to use effective methods of contraception during the study period and within 3 months after the last dose;
7. Prior anti-tumor therapy with a distance of >= 4 weeks between initial administration/radiotherapy, and the toxicity related to anti-tumor therapy has returned to <= 1 level (NCI CTCAE 5.0), except for hair loss, vitiligo, stable hypothyroidism after hormone replacement therapy, etc.;
8. If no blood transfusion, erythropoietin (EPO), recombinant human granulocyte macrophage colony-stimulating factor (G-CSF), granulocyte macrophage colony-stimulating factor (GM-CSF), thrombopoietin (TPO), or other corrections have been received within 7 days before the first dose/radiotherapy, the laboratory test values within 7 days before the first dose/radiotherapy must meet the following conditions:
(1) Blood routine: Absolute neutrophil count >= 1.5 × 10^9/L, white blood cell count >= 3 × 10^9/L, platelet count >= 80 × 10^9/L, hemoglobin >= 90 g/L;
(2) Renal function: serum creatinine <= 1.5 × Upper limit of normal value (ULN) and creatinine clearance rate >= 30 mL/min (calculated by Cockroft Fault formula *);
(3) Liver function: Total bilirubin < 1.5 × ULN, AST, ALT < 2.5 × ULN (if confirmed liver metastasis, AST, ALT < 5 × ULN, total bilirubin < 3 × ULN);
(4) Coagulation function: International standardized ratio (INR) < 1.5 × ULN with activated partial prothrombin time (APTT) < 1.5 × ULN. Subjects receiving full dose oral anticoagulant therapy must receive a stable dosage (at least 14 days); Individuals receiving warfarin treatment must have an INR <= 3.0; Individuals receiving low molecular weight heparin treatment are allowed to be included in the group;
9. After sufficient communication between the researcher and the subject, they voluntarily sign an informed consent form and are willing to follow the experimental treatment plan and visit plan.

排除标准：

1. 已知或筛选期检查发现患有活动性脑转移和/或癌性脑膜炎的患者。但允许以下受试者入组：（1）无症状性脑转移患者（即没有脑转移引起的进行性加重的中枢神经系统症状，不需要使用皮质类固醇，且病灶大小≤ 1.5 cm）可以参加，但需要对疾病部位定期进行脑部影像学检查；（2）经治疗且脑转移病灶稳定至少4周的受试者，没有新的或扩大的脑转移证据，且临床试验用药物给药/放疗前3天停用类固醇。稳定的脑转移应该在临床试验用药物首次给药前确定； 2. 已知或疑似对任何研究用药成分过敏者； 3. 已知患有活动性乙型肝炎[乙肝表面抗原（HBs-Ag）阳性和/或乙肝核心抗体（HBc-Ab）阳性且乙肝病毒脱氧核糖核酸（HBV-DNA）≥ 2800 copies/ml或者≥ 500 IU/ml）]或丙型肝炎病毒核糖核酸（HCV-RNA）阳性、人类免疫缺陷病毒（HIV）抗体、梅毒螺旋体抗体检查结果阳性的受试者； 4. 患者存在不稳定或可能影响其安全性或研究依从性的其他任何疾病或医学状态，任何严重或未控制的系统性疾病，包括严重心脏病、脑血管病、未控制的糖尿病、未控制或用药控制不佳的高血压（收缩压＞ 140 mmHg和/或舒张压＞ 90 mmHg）、严重感染（包括首次给药/放疗前14天内活动性感染）、活动性消化道溃疡、免疫功能异常等； 5. 符合下列任一条件的心脑血管疾病/症状/指征：（1）静息QTcF> 470 ms【经过校正的QT间期（通过Fridericia公式校正），采集静息10分钟后的心电图】；（2）任何有临床意义的重要的静息ECG（心电图）在节律、传导或形态方面的异常，如完全性左束支传导阻滞、2度和3度的心脏传导阻滞、PR间期> 250 ms等；（3）任何增加QTc延长或心律失常风险的因素，如心力衰竭、低钾血症、先天性长QT综合征、长QT综合征家族史，或在40岁以下一级亲属中不明原因的猝死，或任何已知可延长QT间期的合并用药；（4）左室射血分数（LVEF）< 50%；（5）既往有心肌收缩力下降的病史，且在临床试验用药物给药/放疗前6个月内出现过相关症状者：如慢性充血性心力衰竭、肺水肿或心脏射血分数下降等；（6）既往有急慢性心脑血管病史，且在临床试验用药物给药/放疗前6个月内出现过相关症状者：如心肌梗塞、重度或不稳定型心绞痛、脑梗塞、脑出血，或短暂性脑缺血发作等； 6. 合并其他恶性肿瘤或有其他恶性肿瘤病史者，除外既往已得到有效控制的、非侵袭性的、5年无复发转移的皮肤基底细胞癌或鳞状细胞癌，宫颈原位癌和乳腺导管癌； 7. 首次给药/放疗前2周内存在仍无法控制的心包积液、腹腔、胸腔积液等第三间隙积液，研究者判断不适合入组本研究的； 8. 患者需要在首次给药/放疗前2周内使用皮质类固醇（强的松> 10 mg/天或同类药物同等剂量）或其他免疫抑制剂全身治疗的任何病症，但目前或之前曾使用过以下任何类固醇方案的情况除外：肾上腺素替代性类固醇（强的松≤ 10 mg/天或同类药物同等剂量）；全身吸收量极小的局部、眼用、关节内、鼻内或吸入性皮质类固醇；预防性地短期（≤ 7 天）使用皮质类固醇（例如，对造影剂过敏）或用于治疗非自身免疫疾病（例如由接触性过敏原引起的延迟性超敏反应）； 9. 首次给药/放疗前2周内已接种疫苗或计划接种疫苗的患者； 10. 首次给药/放疗前4周内接受过临床研究中的药品或生物类产品治疗，或在本试验期间同时参与任何其他类型的研究； 11. 首次给药/放疗前3个月内有重大外科手术史或者计划在临床试验期间进行重大外科手术者，经研究者判定不宜入组者； 12. 首次给药/放疗前3个月内有献血史或大量出血（大于450 mL）；计划在试验期间或研究结束后3个月内献血或血液成份者； 13. 静脉采血困难或不能耐受静脉穿刺者，不能耐受BM201注射液的局部注射者； 14. 妊娠（妊娠试验结果为阳性）及哺乳期女性； 15. 男性（或其伴侣）或女性受试者自签署知情同意书起至研究结束3个月内有妊娠计划或捐精、捐卵计划，不愿采取有效的避孕措施者； 16. 研究者认为不适合入组的受试者。

Exclusion criteria：

1. Patients who are known to have active brain metastasis and/or cancerous meningitis during the screening period. However, the following subjects are allowed to be enrolled: (1) Asymptomatic brain metastasis patients (i.e. without progressive central nervous system symptoms caused by brain metastasis, no need to use corticosteroids, and lesion size <= 1.5 cm) can participate, but regular brain imaging examinations of the disease site are required; (2) Subjects who have been treated and have stable brain metastases for at least 4 weeks have no evidence of new or expanded brain metastases, and steroids have been discontinued 3 days before drug administration/radiotherapy in clinical trials. Stable brain metastasis should be determined before the first administration of drugs in clinical trials. 2. Individuals who are known or suspected to be allergic to any investigational medication ingredient; 3. Subjects who are known to have active hepatitis B [hepatitis B B surface antigen (HBs Ag) positive and/or hepatitis B core antibody (HBc Ab) positive and hepatitis B virus deoxyribonucleic acid (HBV-DNA) >= 2800 copies/ml or >= 500 IU/ml] or hepatitis C virus ribonucleic acid (HCV-RNA) positive, human immunodeficiency virus (HIV) antibody, treponema pallidum antibody test results positive; 4. The patient has any other disease or medical state that is unstable or may affect his safety or research compliance, any serious or uncontrolled systemic disease, including serious heart disease, cerebrovascular disease, uncontrolled diabetes, uncontrolled or poorly controlled high blood pressure (systolic pressure>140 mmHg and/or diastolic pressure>90 mmHg), serious infection (including active infection within 14 days before the first administration/radiotherapy), active gastrointestinal ulcers, immune dysfunction, etc; 5. Cardiovascular and cerebrovascular diseases/symptoms/indications that meet any of the following conditions: (1) Resting QTcF>470 ms [corrected QT interval (corrected by Fridericia formula), collect electrocardiogram after 10 minutes of rest]; (2) Any clinically significant abnormalities in rhythm, conduction, or morphology of resting ECG (electrocardiogram), such as complete left bundle branch block, 2nd and 3rd degree heart block, PR interval>250 ms, etc; (3) Any factors that increase the risk of QTc prolongation or arrhythmia, such as heart failure, hypokalemia, congenital long QT syndrome, family history of long QT syndrome, or unexplained sudden death in first-degree relatives under the age of 40, or any known combination medication that can prolong the QT interval; (4) Left ventricular ejection fraction (LVEF)<50%; (5) Individuals with a history of decreased myocardial contractility and related symptoms within 6 months prior to drug administration/radiotherapy in clinical trials, such as chronic congestive heart failure, pulmonary edema, or decreased cardiac ejection fraction; (6) Individuals who have a history of acute or chronic cardiovascular and cerebrovascular diseases and have experienced related symptoms within 6 months before drug administration/radiotherapy in clinical trials, such as myocardial infarction, severe or unstable angina, cerebral infarction, cerebral hemorrhage, or transient ischemic attacks; 6. For those who have merged with other malignant tumors or have a history of other malignant tumors, excluding skin basal cell carcinoma or squamous cell carcinoma, cervical carcinoma in situ, and breast ductal carcinoma that have been effectively controlled in the past, non-invasive, and have not recurred or metastasized for 5 years; 7. If there is still uncontrollable third space effusion such as pericardial effusion, abdominal cavity, and pleural effusion within 2 weeks before the first administration/radiotherapy, and the researcher determines that it is not suitable for inclusion in this study; 8. Patients are required to use corticosteroids (prednisone>10 mg/day or equivalent dose of the same drug) or other immunosuppressive agents for systemic treatment of any condition within 2 weeks before the first dose/radiotherapy, except for those who have currently or previously used any of the following steroid regimens: adrenal hormone replacement steroids (prednisone <= 10 mg/day or equivalent dose of the same drug); Local, ocular, intra-articular, with minimal systemic absorption Intranasal or inhaled corticosteroids; Prophylactic short-term (<= 7 days) use of corticosteroids (such as allergies to contrast agents) or for the treatment of non autoimmune diseases (such as delayed hypersensitivity caused by contact allergens); 9. Patients who have received or plan to receive vaccines within 2 weeks before the first dose/radiotherapy; 10. Within 4 weeks prior to the first administration/radiotherapy, have received treatment with drugs or biological products from clinical studies, or have participated in any other type of study during this trial period; 11. Those who have a history of major surgical procedures or plan to undergo major surgical procedures during the clinical trial period within 3 months prior to the first administration/radiotherapy, and have been determined by the researcher to be unsuitable for enrollment; 12. Have a history of blood donation or significant bleeding (greater than 450 mL) within 3 months before the first dose/radiotherapy; Those who plan to donate blood or blood components during the trial period or within 3 months after the end of the study; 13. Those who have difficulty or cannot tolerate venous puncture, and those who cannot tolerate local injection of BM201 injection; 14. Pregnancy (positive pregnancy test results) and lactating women; 15. Male (or her partner) or female subjects who have a pregnancy plan or a sperm or egg donation plan within 3 months from signing the informed consent form to the end of the study and are unwilling to take effective contraceptive measures; 16. Subjects deemed unsuitable for inclusion by the researchers.

研究实施时间：

Study execute time：

从 From 2023-11-15 00:00:00至 To 2025-07-03 00:00:00

征募观察对象时间：

Recruiting time：

从 From 2023-11-30 00:00:00 至 To 2025-01-29 00:00:00

干预措施：

Interventions：

组别：	试验组	样本量：	30
Group：	Experimental group	Sample size：	30
干预措施：	BM201注射液联合信迪利单抗注射液以及放射治疗	干预措施代码：
Intervention：	BM201 injection with sintilimab and radiotherapy	Intervention code：

研究实施地点：

Countries of recruitment and research settings：

国家：	中国	省(直辖市)：	江苏省	市(区县)：	南京市
Country：	China	Province：	Jiangsu	City：	Nanjing
单位(医院)：	南京大学医学院附属南京鼓楼医院	单位级别：	三甲
Institution hospital：	Nanjing Drum Towel Hospital The Affiliated Hospital of Nanjing University Medical School	Level of the institution：	Tertiary A

测量指标：

Outcomes：

指标中文名：	剂量限制性毒性（DLT）	指标类型：	主要指标
Outcome：	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：	最大耐受剂量（MTD）	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：	推荐的联合用药的剂量	指标类型：	主要指标
Outcome：	Recommended dosage for combination medication	Type：	Primary indicator
测量时间点：		测量方法：
Measure time point of outcome：		Measure method：

指标中文名：	安全性评估（生命体征、体格检查、实验室指标、不良事件（AE）、免疫相关不良事件（irAE）、严重不良事件（SAE））	指标类型：	主要指标
Outcome：	Safety assessment (vital signs, physical examination, laboratory indicators, adverse events (AE), immune related adverse events (irAE), severe adverse events (SAE))	Type：	Primary indicator
测量时间点：		测量方法：
Measure time point of outcome：		Measure method：

指标中文名：	注射病灶客观缓解率（ORR）	指标类型：	次要指标
Outcome：	Objective response rate (ORR) of injection lesions	Type：	Secondary indicator
测量时间点：		测量方法：
Measure time point of outcome：		Measure method：

指标中文名：	注射病灶缓解持续时间（DOR）	指标类型：	次要指标
Outcome：	Duration of Remission (DOR) of injection lesions	Type：	Secondary indicator
测量时间点：		测量方法：
Measure time point of outcome：		Measure method：

指标中文名：	注射病灶疾病控制率（DCR）	指标类型：	次要指标
Outcome：	disease control rate (DCR) of injection lesions	Type：	Secondary indicator
测量时间点：		测量方法：
Measure time point of outcome：		Measure method：

指标中文名：	总体客观缓解率（ORR）	指标类型：	次要指标
Outcome：	Objective response rate (ORR)	Type：	Secondary indicator
测量时间点：		测量方法：
Measure time point of outcome：		Measure method：

指标中文名：	总体缓解持续时间（DOR）	指标类型：	次要指标
Outcome：	Duration of Remission (DOR)	Type：	Secondary indicator
测量时间点：		测量方法：
Measure time point of outcome：		Measure method：

指标中文名：	总体疾病控制率（DCR）	指标类型：	次要指标
Outcome：	disease control rate (DCR)	Type：	Secondary indicator
测量时间点：		测量方法：
Measure time point of outcome：		Measure method：

指标中文名：	无进展生存期	指标类型：	次要指标
Outcome：	Progression free survival, PFS	Type：	Secondary indicator
测量时间点：		测量方法：
Measure time point of outcome：		Measure method：

指标中文名：	总生存期	指标类型：	次要指标
Outcome：	Overall survival, OS	Type：	Secondary indicator
测量时间点：		测量方法：
Measure time point of outcome：		Measure method：

指标中文名：	外周血细胞因子（IL6、IL12、TNF-α、IFN-γ）	指标类型：	附加指标
Outcome：	Peripheral blood cytokines (IL-6/IL-12/TNF-α/IFN-γ)	Type：	Additional indicator
测量时间点：		测量方法：
Measure time point of outcome：		Measure method：

指标中文名：	PD-L1 表达情况	指标类型：	附加指标
Outcome：	PD-L1 expression status	Type：	Additional indicator
测量时间点：		测量方法：
Measure time point of outcome：		Measure method：

指标中文名：	免疫微环境检测	指标类型：	附加指标
Outcome：	Immunological microenvironment detection	Type：	Additional 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：	组织	组织：
Sample Name：	tissue	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	75	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)：

NA

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：	NA

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）：	NA
The way of sharing IPD”(include metadata and protocol, If use web-based public database, please provide the url)：	NA
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系统进行数据采集和管理。
Data collection and Management (A standard data collection and management system include a CRF and an electronic data capture：	EDC system for data collection and management.
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：	2023-11-24 11:40:44