ChiCTR2300078987 版本V1.0 版本创建时间2023/12/22 10:52:16 中国临床试验注册中心

审核状态：

Project audit state：

通过审核

Successful

注册号：

Registration number：

 ChiCTR2300078987 

最近更新日期：

Date of Last Refreshed on：

 2023-12-22 10:51:48 

注册时间：

Date of Registration：

 2023-12-22 00:00:00 

注册号状态：

预注册

Registration Status：

Prospective registration

注册题目：

一项在晚期实体瘤患者中评估基因改造的减毒沙门氏菌SGN1瘤内注射给药的安全性和耐受性的I/IIa期、开放性、剂量递增和剂量扩展研究

Public title：

A Phase I/IIa, Open-label, Dose-Escalation and Dose-Expansion Study to Evaluate the Safety and Tolerability of Modified Salmonella Typhimurium SGN1 Administered via Intratumoral Injection 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：

一项在晚期实体瘤患者中评估基因改造的减毒沙门氏菌SGN1瘤内注射给药的安全性和耐受性的I/IIa期、开放性、剂量递增和剂量扩展研究

Scientific title：

A Phase I/IIa, Open-label, Dose-Escalation and Dose-Expansion Study to Evaluate the Safety and Tolerability of Modified Salmonella Typhimurium SGN1 Administered via Intratumoral Injection 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：

郑莉 

研究负责人：

郑莉,刘磊 

Applicant：

Li Zheng 

Study leader：

Li Zheng, Lei Liu 

申请注册联系人电话：

Applicant telephone：

 +86 189 8060 1950

研究负责人电话：

Study leader's
telephone：

+86 189 8060 1950

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：

 18980601950@163.com

研究负责人电子邮件：

Study leader's E-mail：

 18980601950@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：

中国四川省成都市武侯区国学巷37号

研究负责人通讯地址：

中国四川省成都市武侯区国学巷37号

Applicant address：

No. 37, Guoxue Alley, Wuhou District, Chengdu, Sichuan, China

Study leader's address：

No. 37, Guoxue Alley, Wuhou District, Chengdu, Sichuan, China

申请注册联系人邮政编码：

Applicant postcode：

 610041

研究负责人邮政编码：

Study leader's postcode：

 610041

申请人所在单位：

四川大学华西医院

Applicant's institution：

West China Hospital of Sichuan University

研究负责人所在单位：

四川大学华西医院

Affiliation of the Leader：

West China Hospital of Sichuan University

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年临床试验(西药)审(266)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：

四川大学华西医院临床试验伦理审查委员会

Name of the ethic committee：

Ethics Committee on Clinical Trial,West China Hospital of Sichuan University

伦理委员会批准日期：

Date of approved by ethic committee：

 2023-09-06 00:00:00

伦理委员会联系人：

韩玉榕、董一君、侯敏

Contact Name of the ethic committee：

Yurong Han, Yijun Dong, Min Hou

伦理委员会联系地址：

中国四川省成都市武侯区国学巷37号，邮编610041

Contact Address of the ethic committee：

No. 37, Guoxue Alley, Wuhou District, Chengdu, Sichuan, 610041, China

伦理委员会联系人电话：

Contact phone of the ethic committee：

 +86 28 8542 3237

伦理委员会联系人邮箱：

Contact email of the ethic committee：

 huaxilunli@wchscu.cn

研究实施负责（组长）单位：

四川大学华西医院

Primary sponsor：

West China Hospital of Sichuan University

研究实施负责（组长）单位地址：

中国四川省成都市武侯区国学巷37号，邮编610041

Primary sponsor's address：

No. 37, Guoxue Alley, Wuhou District, Chengdu, Sichuan, 610041, 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)：

广东省

市(区县)：

广州市

Country：

China

Province：

Guangdong

City：

Guangzhou

单位(医院)：

广州华津医药科技有限公司

具体地址：

中国广州市黄埔区开源大道11号C5栋101室

Institution
hospital：

Guangzhou Sinogen Pharmaceutical Co., Ltd.

Address：

Room 101, Building C5, No.11 Kaiyuan Avenue, Huangpu District, Guangzhou, China

经费或物资来源：

广州华津医药科技有限公司

Source(s) of funding：

Guangzhou Sinogen Pharmaceutical Co., Ltd.

研究疾病：

晚期实体瘤  

Target disease：

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+II期 

Study phase：

1-2

研究设计：

单臂 

Study design：

Single arm 

研究目的：

第1 部分 主要目的： 评估SGN1瘤内注射在晚期实体瘤患者中的安全性和耐受性。 次要目的： 初步确定最大耐受剂量（MTD）和最佳生物剂量（OBD）。 分析并描述SGN1的PK特征。 评估SGN1的细菌脱落。 评估SGN1瘤内注射在晚期实体瘤患者中的初步疗效。 评估其他安全性指标。 探索性目的： Choi标准评估的肿瘤治疗疗效。 第2部分： 主要目的： 评估SGN1在特定肿瘤亚型中的初步疗效。 次要目的： 评估SGN1在特定肿瘤亚型中的安全性。 分析和描述SGN1的PK特征。 评估SGN1的细菌脱落。 评估其他安全性指标。 探索性目的： 根据肿瘤类型探索相应的肿瘤生物标志物。 Choi标准评估的肿瘤治疗疗效  

Objectives of Study：

Part 1 Primary Objectives: To evaluate the safety and tolerability of intratumoral injection of SGN1 in patients with advanced solid tumor. Secondary Objectives: To make a preliminary determination of the Maximum Tolerated Dose (MTD) and optimal biological doses (OBD). To analyze and describe the PK profile of SGN1. To evaluate bacterial shedding of SGN1. To evaluate the preliminary efficacy of SGN1intratumoral injection in patients with advanced solid tumor. To evaluate additional safety measures. Exploratory Objectives: Efficacy assessed by Choi criteria. Part 2: Primary Objectives: To evaluate the preliminary efficacy of SGN1 in specific tumor subtypes. Secondary Objectives: To evaluate the safety of SGN1 in specific tumor types. To analyze and describe the PK profile of SGN1. To evaluate bacterial shedding of SGN1. To evaluate additional safety measures. Exploratory Objectives: Tumor biomarkers upon tumor types. Efficacy assessed by Choi criteria.

药物成份或治疗方案详述：

 

Description for medicine or protocol of treatment in detail：

 

纳入标准：

1. 签署知情同意书时年龄在18～75岁之间，男女不限； 2. 第1部分：以标准治疗失败（疾病进展或不耐受，如化疗、靶向治疗和其他免疫治疗）为特征的晚期（不可切除或转移性）癌症（包括但不限于小细胞肺癌、非小细胞肺癌（腺癌和鳞癌）、霍奇金淋巴瘤或非霍奇金淋巴瘤、肉瘤、宫颈癌、黑色素瘤、头颈癌、乳腺癌、卵巢癌、腹膜假粘液瘤（PMP）和肝细胞癌）患者或无标准治疗选择的患者或不耐受标准治疗的患者； 注：所有肿瘤类型的标准治疗均参照现行版CSCO/NCCN 指南。 标准治疗失败指患者在接受CSCO/NCCN 指南推荐的标准治疗时出现疾病进展，或在接受标准治疗后复发/转移。 无标准治疗指接受过指南推荐的治疗，且目前无其他有效治疗方案的患者。 3. 第2部分：特定肿瘤类型扩展研究可招募以下患者： HNSCC、肉瘤、HCC、宫颈癌、黑色素瘤或在第1部分观察到潜在疗效信号的其他肿瘤类型患者，标准治疗失败或对标准治疗不耐受； 4. 患者必须有适合局部注射SGN1的主病灶。肿瘤须为皮下可触及或可在彩色多普勒超声引导下（优选），如果研究者认为有必要，也可以在CT引导下注射肿瘤。由具有资质且接受过培训的介入放射科医生或专家直接注射的原位或转移性实体瘤，且这些肿瘤预先经影像学检查确认未侵袭血管壁或空腔脏器。如果研究者在治疗过程中判断肿瘤内部存在液化，建议使用超声波检查肿瘤内部液化情况。 5. 美国东部肿瘤协作组（ECOG）体能状态评分为0～1分； 6. 预期生存期≥12周； 7. 患者已从既往用药引起的任何毒性反应中恢复（根据NCI-CTCAE 5.0版，≤1级，以下除外：a.脱发；b.色素沉着；c.放疗引起的长期毒性，且经研究者判定为无法恢复；d.铂类药物引起的≤2级神经毒性；e.血红蛋白在90～100 g/L[包括边界值]）或研究者评估认为患者病情稳定。 8. 根据RECIST 1.1确定至少有一个可测量的病灶（对于实体瘤）； 9. 实验室检查必须符合以下要求，且患者在检查前14天内不得接受任何血细胞生长因子，在筛选前14天内不得接受输血（允许实验室检查值超出规定范围的患者在筛选期间重新检查，以符合标准）： a) 中性粒细胞绝对计数（ANC）≥1.5×109 /L，血小板≥75×109 /L；血红蛋白≥90 g/L； b) 血清白蛋白≥30 g/L；胆红素≤1.5×ULN，ALT和AST≤2.5×ULN； c) 对于肝转移患者，ALT和AST≤5×ULN； d) 肌酐清除率≥50 mL/min（标准Cockcroft -Gault公式）或Cr≤1.5×ULN：尿蛋白≤2＋或尿蛋白定量＜1.0 g/L； e) 凝血功能的国际标准化比值（INR）≤1.5×ULN，活化部分凝血活酶时间（APTT）≤1.5×ULN（如果患者合并使用抗凝剂，则凝血功能是否合格将由研究者判断） 10. 如果是女性，需绝经后至少1年并记录卵泡刺激素（FSH）＞30 IU/L，或手术绝育至少3个月，对于有生育能力的女性，必须通过血液和尿妊娠试验证实未妊娠，且处于非哺乳期。 11. 有生育能力的女性患者必须同意从签署知情同意书至最后一次研究药物瘤内注射后至少6个月内采用可接受的避孕方法。 12. 有生殖能力的男性患者必须同意从开始动员至最后一次研究药物瘤内注射后至少6个月内采用有效的避孕措施。 13. 患者在治疗后能够参加随访。 14. 患者能够理解并自愿签署知情同意书。

Inclusion criteria

1. Male or females aged 18~75 years at the time of informed consent; 2. Part 1: Patients with advanced stage (unresectable or metastatic) cancer including but not limited to small cell lung cancer, non-small cell lung cancer (adeno- and squamous), Hodgkin’s lymphoma or non-Hodgkin’s lymphoma, sarcoma, cervical carcinoma, Melanoma, head and neck cancer, breast cancer, ovarian cancer, pseudomyxoma peritoneum (Pseudomyxoma peritonei, PMP) and hepatocellular carcinoma characterized by failure to standard treatment (disease progression or intolerance, such as chemotherapy, targeted therapy, and other immunotherapies) or patients who have no standard treatment options or patients who are intolerable to standard treatment; Note: For all tumor species included, standard treatment will refer to current Chinese Society of Clinical Oncology (CSCO)/National Comprehensive Cancer Network (NCCN) guidelines. Standard treatment failure refers to patients who have disease progression after the existing standard of care recommended by CSCO/NCCN guidelines, or relapse/metastasis after standard of care. Non-standard treatment refers to patients who have received the treatment recommended by the guidelines and currently have no other effective treatment options. 3. Part 2: the specific tumor-type expansion study may enroll the following patients: Patients with advanced HNSCC, Sarcoma, HCC, cervical cancer, melanoma, or other tumor type with potential efficacy signal observed in Part 1, who have failed standard therapy or who areintolerant to standard treatment; 4. Patients must have a main lesion suitable for local injection of SGN1. The tumors must be in situ or metastatic solid tumors that are subcutaneous, palpable, or can be injected directly using methods including but not limited to color doppler ultrasound guidance, which is the preferred method. If the Investigator(s) judge(s) it necessary, the tumor can also be injected under CT guidance by an interventional radiologist or specialist with adequate qualifications and trainings, provided that these tumors do not invade the walls of blood vessels or hollow organs confirmed by previous imaging studies. If there is liquefaction inside the tumor judged by the Investigator during treatment, it is recommended to use ultrasound to check the internal liquefaction of the tumor. 5. Eastern Cooperative Oncology Group (ECOG) performance status score of 0-1; 6. Life expectancy ≥ 12 weeks; 7. Patients have recovered from any toxic reaction to previous medications [≤Grade 1 based on NCICTCAE v 5.0, except a. Hair loss; b. Pigmentation; c. The long-term toxicity caused by radiotherapy and cannot be recovered by the Investigator’s judgment; d. Platinum induced neurotoxicity of grade 2 and below; e. Hemoglobin at 90 ~ 100 g/L (including boundary value)] or stable status assessed by the Investigator. 8. At least one measurable lesion as determined by RECIST 1.1(for solid tumors); 9. Laboratory tests must meet the following requirements and patient must not have received any blood cell growth factor 14 days before the test and no blood transfusions within 14 days prior to screening (patients with laboratory values outside of the specified ranges will be permitted to be retested during the screening period in order to meet the criteria)]: a) absolute count of neutrophils (ANC) ≥1.5×109 /L, platelet ≥75×109 /L; Hemoglobin ≥90 g/L; b) serum albumin ≥ 30 g/L; Bilirubin ≤1.5 × ULN, ALT and AST ≤2.5 × ULN; c) In patients with liver metastasis, ALT and AST≤5 × ULN; d) Creatinine clearance ≥50 mL/min (standard Cockcroft -Gault formula) or Cr ≤1.5 ×ULN: urinary protein ≤2+ or urinary protein quantitative <1.0 g/L; e) International standardized ratio of coagulation function (INR) ≤ 1.5 × ULN, activated partial thromboplastin time (APTT) ≤ 1.5 × ULN (if the patient is taking concomitant anticoagulant medication, whether the coagulation function is qualified will be determined by the Investigator). 10. If female, be either postmenopausal for at least 1 year with documented follicle stimulating hormone (FSH) >30 IU/L, or surgically sterile for at least 3 months, or if a woman of childbearing potential, must be non-pregnant confirmed by blood and urine pregnancy tests, and non-lactating 11. Female patients of childbearing potential must agree to use acceptable method(s) of contraception from consent through at least 6 months after the last dose of drug intratumoral injection. 12. Male patients of reproductive capacity must agree to use effective contraception from start of mobilization through at least 6 months after the last dose of drug intratumoral injection 13. Patients must be able to follow up after the treatment 14. Patients must understand and voluntarily sign the informed consent form.

排除标准：

1. 曾接受过溶瘤细菌治疗； 2. 肿瘤病灶极大的患者（单个肿瘤的最长直径超过8 cm），多发病灶不适合接受瘤内注射的患者（主要是指广泛转移，不适合局部治疗的患者）； 3. 对沙门氏菌敏感抗生素过敏或不耐受，或合并感染性疾病且目前正在使用抗生素； 4. 空腔脏器（胃、食管、肠、尿道等）目前存在可评估肿瘤； 5. 已知对研究药物或其任何辅料或解救药物过敏的患者；或对其他单克隆抗体有严重过敏反应的患者； 6. 在首次接受研究药物治疗之前接受过以下治疗或药物的患者： a) 在首次接受研究药物治疗前28天内进行过大手术（允许接受以诊断为目的的活检）； b) 在首次接受研究药物治疗前14天内接受过免疫抑制药物（泼尼松＞10 mg/天，地塞米松＞1.5 mg/天），不包括皮质类固醇鼻喷剂和吸入性皮质类固醇或生理剂量的全身用皮质类固醇（即不超过10 mg/d的泼尼松或同等生理剂量的其他皮质类固醇）； c) 接种（减毒）活病毒疫苗：在研究药物首次给药前28天内，或研究期间，或研究药物末次给药后60天； d) 在研究药物首次给药前28天内接受过任何抗肿瘤治疗（包括化疗、放疗、免疫治疗、内分泌治疗、靶向治疗、生物治疗或肿瘤栓塞）（如果接受亚硝基脲或丝裂霉素化疗，则化疗结束与研究治疗首次给药之间的间隔不得少于6周）； 7. 已知存在无法控制或症状性活动性CNS转移，表现为有临床症状、脑水肿、脊髓压迫、癌性脑膜炎、软脑膜疾病和/或进行性生长的患者。有中枢神经系统转移史或脊髓压迫史的患者，如果明确接受过治疗，并在研究药物首次给药前停用抗惊厥药和类固醇后连续4周显示稳定的临床表现，则可纳入本研究； 8. 筛选时存在憩室炎或可能促进非靶病灶中厌氧菌意外生长的疾病； 9. 肿瘤已扩散至内脏，在短期内有出现危及生命的并发症（包括无法控制的大量积液[胸腔、心包腔或腹腔]）风险的症状性晚期患者； 10. 患有任何活动性自身免疫性疾病或有任何可预测复发的自身免疫性疾病史的患者（包括但不限于：自身免疫性肝炎、间质性肺炎、葡萄膜炎、肠炎、肝炎、垂体炎、血管炎、肾炎、甲状腺功能亢进症、甲状腺功能减退症[通过激素替代疗法就能控制病情的患者可以入选]；患有不需要全身治疗的皮肤病（如白癜风、银屑病、脱发、I型糖尿病）患者，或患有儿童哮喘在成年后已完全缓解且不需要干预的患者可以入选。需要支气管扩张剂进行医学干预的哮喘患者不能入选）； 11. 进入研究前2年内有其他活动性恶性肿瘤的患者。有宫颈原位癌、浅表性或非侵袭性膀胱癌或基底细胞或鳞状细胞原位癌病史，既往接受过根治性治疗的患者可根据研究者的判断入选； 12. 人类免疫缺陷病毒（HIV）感染或已知有获得性免疫缺陷综合征（AIDS），未经治疗的活动性肝炎（乙型肝炎，定义为：乙型肝炎病毒表面抗原[HBsAg]检测阳性，HBV-DNA≥500 IU/mL且肝功能异常；丙型肝炎，定义为；丙型肝炎抗体[HCV-Ab]检测阳性，HCV-RNA高于检测下限且肝功能异常）或乙型肝炎和丙型肝炎合并感染； 13. 存在无法有效控制的心脏临床症状或疾病，如： a) NYHA 2级或以上心力衰竭； b) 不稳定型心绞痛； c) 1年内发生心肌梗死； d) 需要治疗或干预的有临床意义的室上性或室性心律失常患者； e) 药物治疗后（收缩压）≥160 mmHg且（舒张压）≥100 mmHg的未受控制的高血压； f) 患有心脏瓣膜病或二尖瓣脱垂、主动脉瓣疾病或其他心脏血流紊乱的患者。 14. 在研究药物首次给药之前存在活动性或未控制的感染或不明原因的发热（＞38.5℃）的患者（根据研究者的判断，可纳入肿瘤引起的发热）； 15. 可能导致厌氧菌繁殖的憩室炎； 16. 6个月内有沙门氏菌感染记录； 17. 已知有异体器官移植或异体造血干细胞移植史； 18. 参加其他临床研究或在入组前4周（或其他研究药物的5个半衰期，以较长者为准）内参加过其他临床研究并接受试验药物给药的患者； 19. 已知有精神类药物滥用或娱乐性药物滥用史； 20. 根据研究者的判断，存在其他可能导致终止的因素，如经治疗后仍存在肾上腺皮质功能不全、垂体功能不全和其他严重疾病（包括精神疾病）、实验室检查存在严重异常、家庭或社会因素，这些因素可能影响患者安全或检查数据和样本采集； 21. 在首次试验治疗前28天内接种过疫苗，灭活疫苗和RNA疫苗（例如灭活流感疫苗和COVID-19 RNA疫苗）除外； 22. 植入起搏器、人工心脏瓣膜或金属骨科假体等植入物的患者（在第2部分中不排除有血管植入物的患者）； 23. 根据研究者的判断，患者由于其他原因不适合参加研究； 24. 筛选时6个月内发生过肠梗阻或腹部立位平片或腹部CT提示有肠梗阻的可能，或研究者认为有肠梗阻的风险者。

Exclusion criteria：

1. Prior treatment with oncolytic bacteria; 2. Patients with extremely large tumor (the longest diameter of a single tumor exceeds 8 cm); patients with multiple lesions cannot receive intratumoral injection, it mainly refers to patients with extensive metastasis who are not suitable for local treatment; 3. Patients who are allergic or intolerant to salmonella sensitive antibiotics, and have infectious diseases and are currently using antibiotics; 4. Present assessable tumors in hollow organs (stomach, esophagus, intestine, urinary tract etc.). 5. Patients who are known to be allergic to the investigational drug or any of its excipients, or rescue medications; or have a severe allergic reaction to other monoclonal antibodies; 6. Patients who have received the following treatments or drugs before the first treatment with the investigational drug: a) Major surgery performed within 28 days before the first treatment with the investigational drug (biopsy is allowed for diagnostic purposes); b) Immunosuppressive drugs have been administered within 14 days before the first treatment with the investigational drug (Prednisone >10 mg/day, Dexamethasone >1.5 mg/day), excluding corticosteroid nasal sprays and inhaled corticosteroids or physiological doses of systemic steroid hormones (i.e., prednisone not exceeding 10 mg/d or equivalent physiological doses of other corticosteroids); c) Inoculation of (attenuated) live virus vaccine: within 28 days before the first dosing of study drug, or during the study period or 60 days after the last dose of study drug; d) Any anti-tumor therapies (including chemotherapy, radiotherapy, immunotherapy, endocrine therapy, targeted therapy, biological therapy or tumor embolization) within 28 days before the first dosing of the investigational drug (if nitrosourea or mitomycin chemotherapy the interval between end of chemotherapy and first dose of study treatment must be no less than 6 weeks); 7. Patients with known uncontrollable or symptomatic active CNS metastases, manifested by clinical symptoms, brain edema, spinal cord compression, cancerous meningitis, leptomeningeal disease, and/or progressive growth. Patients with a history of metastases to the central nervous system or spinal cord compression can be included in the study if they have clearly received treatment and have shown stable clinical manifestations after the discontinuation of anticonvulsants and steroids for 4 weeks before the first dose of the investigational drug; 8. Present with diverticulitis or conditions at screening that might promote the unintentional growth of anaerobic bacteria in nontarget lesions; 9. Symptomatic, advanced patients whose tumors have spread to the internal organs and are at risk of life-threatening complications in the short term (including patients with uncontrollable large amounts of effusion (thoracic cavity, pericardial cavity, or abdominal cavity); 10. Patients with any active autoimmune diseases or a history of any autoimmune disease with predictable recurrence (including but not limited to: autoimmune hepatitis, interstitial pneumonia, uveitis, enteritis, hepatitis, hypophysitis, vasculitis, nephritis, hyperthyroidism, hypothyroidism [only patients whose condition can be controlled by hormone replacement therapy can be included]; Patients with skin diseases that do not require systemic treatment such as vitiligo, psoriasis, hair loss, Type I diabetes mellitus, or those with childhood asthma which has been completely relieved and requires no interventions in adulthood, can be included. Those with asthma who need bronchodilators for medical intervention cannot be included); 11. Patients with other active malignant tumor(s) within 2 years before entering the study. Patients with history of cervical carcinoma in situ, superficial or non-invasive bladder cancer or basal cell or squamous cell cancer in situ previously treated with curative intent may be included at the judgment of the Investigator; 12. Human immunodeficiency virus (HIV) infection or known acquired immunodeficiency syndrome (AIDS), untreated active hepatitis (hepatitis B, defined as: hepatitis B virus surface antigen [HBsAg] testing positive, HBV-DNA ≥ 500 IU/mL and abnormal liver function; hepatitis C, defined as: hepatitis C antibody [HCV-Ab] testing positive, higher HCV-RNA than the lower limit of detection of the analysis method and abnormal liver function) or hepatitis B and hepatitis C co-infection; 13. Existing cardiac clinical symptoms or diseases that cannot be well controlled, such as: a) NYHA grade 2 or above heart failure; b) Unstable angina pectoris; c) Myocardial infarction occurred within 1 year; d) Patients with supraventricular or ventricular arrhythmias that have clinical significance and need treatment or intervention; e) Uncontrolled hypertension (systolic blood pressure) ≥160 mmHg and (diastolic blood pressure) ≥100 mmHg after drug treatment; f) Patients with valvular heart disease or mitral valve prolapse, aortic valve disease or other source of turbulent cardiac blood flow. 14. Patients with active or uncontrolled infection or fever > 38.5°C of unknown cause or before the first administration of the study drug (according to the judgment of the researcher, fever caused by tumor can be included); 15. Diverticulitis that may cause anaerobic bacteria to multiply; 16. Documented salmonella infection within 6 months; 17. Known history of allogeneic organ transplant or allogeneic hematopoietic stem cell transplant; 18. Patients participating in other clinical studies or participating in other clinical studies within 4 weeks or 5 half-lives of other study drugs, whichever is longer, prior to enrollment and receiving experimental drug administration; 19. Known history of psychotropic drug abuse or recreational drug abuse; 20. In the judgment of the Investigator, there are other factors that may lead to termination: for example, adrenal cortex insufficiency, pituitary insufficiency after treatment, and other serious diseases (including mental diseases) serious abnormalities in laboratory examination, family or social factors, that may affect the safety of the patients or test data and sample collection; 21. Vaccination within 28 days of the first trial treatment, except for administration of inactivated vaccines and RNA vaccines (e.g., inactivated influenza vaccines and COVID-19 RNA vaccines); 22. Patients with implants such as pacemakers, prosthetic cardiac valves, or metal orthopedic prostheses (this does not include vascular implants for Part 2); 23. In the Investigator’s judgment, patients who are not suitable for other reasons; 24. Abdominal standing position plain film or abdominal CT indicates the possibility of bowel obstruction within 6 months from screening, or the Investigator believes there is a risk of bowel obstruction.

研究实施时间：

Study execute time：

从 From 2023-12-22 00:00:00至 To 2027-12-31 00:00:00  

征募观察对象时间：

Recruiting time：

从 From 2023-12-22 00:00:00 至 To 2027-12-31 00:00:00

干预措施：

Interventions：

组别：

试验组

样本量：

 70

Group：

Test group

Sample size：

干预措施：

本研究中，SGN1将通过瘤内注射方式注入病灶内。根据剂量水平，给药剂量将为 0.5×10^8 CFU、1×10^8 CFU、2×10^8 CFU、4×10^8 CFU、6×10^8 CFU（可选）。每个剂量组中患者的计划剂量见表6.2.1-1。患者将每周给药一次，连续给药3周，然后停药1周，每28天为1个治疗周期。给药持续至疾病进展。

干预措施代码：

Intervention：

In this study, SGN1 will be injected into the target lesion intratumorally. According to the dose levels, the administered dose will be 0.5×10^8 CFU, 1×10^8 CFU, 2×10^8 CFU, 4×10^8 CFU, 6×10^8 CFU (optional). The planned dosage for the patients from each cohort is presented in Table 6.2.1-1. The patient will be administered once every week for 3 consecutive weeks followed by 1-week rest in 28-day treatment cycles. The duration of administration is until disease progression.

Intervention code：

研究实施地点：

Countries of recruitment and research settings：

国家：

 中国

省(直辖市)：

 四川省 

市(区县)：

 成都市 

Country：

China

Province：

Sichuan

City：

Chengdu

单位(医院)：

 四川大学华西医院 

单位级别：

 三甲 

Institution
hospital：

West China Hospital of Sichuan University

Level of the institution：

Tertiary A

测量指标：

Outcomes：

指标中文名：

客观缓解率

指标类型：

主要指标

Outcome：

ORR

Type：

Primary indicator

测量时间点：

测量方法：

Measure time point of outcome：

Measure method：

指标中文名：

疾病控制率

指标类型：

主要指标

Outcome：

DCR

Type：

Primary 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：

主要指标

Outcome：

PFS

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

指标类型：

次要指标

Outcome：

Safety

Type：

Secondary indicator

测量时间点：

测量方法：

Measure time point of outcome：

Measure method：

指标中文名：

药代动力学

指标类型：

次要指标

Outcome：

PK

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：

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：

唾液

组织：

Sample Name：

Saliva

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：

粪便

组织：

Sample Name：

feces

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)：

None

是否公开试验完成后的统计结果:

Calculated Results after the Study Completed public access:

公开/Public

盲法：

Blinding：

试验完成后的统计结果（上传文件）：

Calculated Results after
the Study Completed(upload file)：

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）：

不适用

The way of sharing IPD”(include metadata and protocol, If use web-based public database, please provide the url)：

Not applicable

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：

有/Yes

注册人：

Name of Registration：

  2023-12-22 10:51:48