肿瘤细胞治疗研究
英文原题：Exploratory Clinical Study of Claudin18.2-Targeted Activated DC and CAR-T Therapy in Advanced Pancreatic Cancer.
这是一项早期 I 期注册临床试验，评估 Claudin18.2 树突状细胞治疗胰腺癌的安全性、可行性及初步疗效。当前状态：招募中。计划入组 10 例。试验地点：中国 · 海口（共 1 个中心，其中中国 1 个）。登记号：NCT07416240。
不限性别 · ≥ 18 Years 且 ≤ 80 Years
纳入标准： 1. 年龄≥18岁且≤80岁，性别不限。 2. 组织学或细胞学确诊晚期胰腺癌，至少有1个符合RECIST 1.1标准的可测量病灶（螺旋CT最长径≥10 mm，或淋巴结短轴≥15 mm）。 3. 肿瘤组织Claudin 18.2免疫组化阳性，表达强度≥2+且表达比例≥50%。 4. 符合外周血单个核细胞（PBMC）采集条件，且无其他细胞采集禁忌证。 5. 二线标准治疗失败、无标准治疗方案，或签署拒绝化疗的文件。 6. ECOG体能状态0–1分，预期生存期≥3个月。 7. 既往化疗及其他抗肿瘤治疗毒性已经过洗脱期并恢复（残留脱发除外），各项功能指标符合入组要求。 8. 器官功能充分：淋巴细胞绝对计数（ALC）≥0.5×10⁹/L、ANC≥1.0×10⁹/L、单核细胞≥0.1×10⁹/L；血小板≥75×10⁹/L、血红蛋白≥90 g/L，血常规检查前14天内未输血或使用G-CSF、促血小板生成素、促红细胞生成素；总胆红素<ULN的2倍，AST和ALT<ULN的2.5倍；肌酐≤ULN的1.5倍；凝血酶原时间（PT）或APTT<ULN的1.5倍，INR<1.5。 9. 有生育能力者愿意采取避孕措施。 10. 能充分理解并愿意签署知情同意书。 11. 愿意遵守访视安排、用药计划、实验室检查及其他试验程序。 排除标准： 1. 存在需立即治疗的肿瘤急症，如恶性心包积液或心脏压塞、上腔静脉阻塞综合征、脊髓压迫等。 2. 有显著心血管疾病，包括过去6个月内发生心肌梗死、心绞痛、心力衰竭、严重心律失常，或接受过血管成形术、支架置入、冠状动脉旁路移植术；或有临床意义的QT间期延长（女性QTcF>470 ms，男性>450 ms）。 3. 有临床意义的出血倾向或凝血障碍，如血友病。 4. HIV、梅毒、乙肝或丙肝感染。 5. 曾因精神疾病被非自愿收治，或治疗医生认为存在不适合治疗的其他精神疾病。 6. 合并其他自身免疫病，或长期使用免疫抑制剂/类固醇。 7. 研究者评估认为依从性差。 8. 本次CAR-T治疗前3个月内曾接受任何靶向CAR-T治疗。 9. 存在无法控制的活动性细菌或真菌感染。 10. 医生认为需要排除的其他情况。
Inclusion Criteria: 1. Age ≥ 18 years, upper limit ≤ 80 years, gender not limited; 2. Participants must have a histologically or cytologically confirmed diagnosis of advanced pancreatic cancer, with at least one measurable lesion meeting RECIST v1.1 criteria (i.e., a target lesion with a longest diameter ≥10 mm on spiral CT scan, or a lymph node with a short axis ≥15 mm). 3. Tumor tissue positive for Claudin 18.2 by immunohistochemical detection (expression intensity ≥ 2+; expression range ≥ 50%); 4. Meeting the indications for PBMC collection and having no other contraindications for cell collection; 5. Failure of standard second-line treatment or lack of a standard treatment regimen; or signing a refusal to undergo chemotherapy. 6. ECOG score: 0-1; 7. Life expectancy: ≥ 3 months; 8. Toxic reactions from previous chemotherapy and other anti-tumor treatments must be resolved through a washout period (except for residual hair loss), ensuring that all functional parameters meet the inclusion criteria; 9. Sufficient organ function, including: 1. Sufficient immune function, i.e., absolute lymphocyte count (ALC) ≥ 0.5 × 10⁹/L, absolute neutrophil count (ANC) ≥ 1.0 × 10⁹/L, monocyte count ≥ 0.1 × 10⁹/L. 2. Sufficient hematopoietic function, i.e., platelet count ≥ 75 × 10⁹/L, hemoglobin ≥ 90 g/L. Patients must not have received blood transfusions or treatments such as granulocyte colony-stimulating factor, thrombopoietin, or erythropoietin within 14 days prior to the complete blood count examination. c) Sufficient liver function, i.e., total bilirubin (TBIL) \< 2 × upper limit of normal (ULN), aspartate aminotransferase (AST) and alanine aminotransferase (ALT) \< 2.5 × ULN. d) Sufficient kidney function, i.e., creatinine (Cr) ≤ 1.5 × ULN. e) Sufficient coagulation function, i.e., prothrombin time (PT) or activated partial thromboplastin time (APTT) \< 1.5 × ULN, and international normalized ratio (INR) \< 1.5. 10. Individuals of fertility must be willing to use contraception; 11. Sufficient understanding and willingness to sign an informed consent form; 12. Willingness to comply with visit schedules, medication plans, laboratory tests, and other trial procedures. Exclusion Criteria: 1. Emergency oncological conditions requiring immediate treatment, such as malignant pericardial effusion or tamponade, superior vena cava obstruction syndrome, spinal cord compression, etc. 2. Significant cardiovascular disease, such as: 1. • A confirmed cardiovascular event within the past 6 months, such as myocardial infarction, angina pectoris, heart failure, severe arrhythmia, or previous angioplasty, stent implantation, or coronary artery bypass grafting; 2. • Clinically significant QT interval prolongation (QTcF \> 470ms for women or QTcF \> 450ms for men). 3. Clinically significant bleeding tendency or coagulation disorders, such as hemophilia; 4. HIV infection, syphilis infection, hepatitis B infection, or hepatitis C infection. 5. History of involuntary custody due to mental illness or other mental illness deemed unsuitable for treatment by the treating physician; 6. Accompanied by other autoimmune diseases, or long-term use of immunosuppressants or steroids; 7. Poor patient compliance as assessed by the investigator; 8. Previous treatment with any target CAR-T within 3 months prior to this CAR-T treatment; 9. Uncontrollable active bacterial or fungal infections; 10. Other conditions deemed necessary to be ruled out by the physician.
以上为辅助阅读译文。是否适合入组须由主治医生判断，最终以登记平台与研究者确认为准。
主要终点：Adverse Events (AEs) · Incidence and severity of adverse events · 2 years
次要终点：Objective Response Rate (ORR)；Disease Control Rate (DCR)；Progression-free survival (PFS)；Changes in the Immune Microenvironment
本开放标签、单臂临床研究旨在评估Claudin18.2靶向活化树突状细胞（DC）联合CAR-T细胞治疗晚期胰腺癌患者的安全性和初步疗效。该联合方案旨在激活DC并精准靶向肿瘤部位，重塑肿瘤免疫微环境、削弱免疫抑制屏障，使CAR-T细胞更有效地深入肿瘤并持续杀伤癌细胞。
This is an open-label, single-arm clinical study designed to evaluate the safety and preliminary efficacy of Claudin18.2 Targeted Activated DC combined with CAR-T therapy in patients with Advanced Pancreatic Cancer. This combination therapy activates dendritic cells (DCs) to precisely target the tumor site, reshaping the tumor immune microenvironment, breaking down the immunosuppressive barrier, and allowing CAR-T cells to penetrate deeper into the tumor more efficiently, precisely and persistently killing cancer cells.
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