肿瘤细胞治疗研究
英文原题：Dual-targeting CLDN18.2 and PD-L1 CAR-T for Patients with CLDN18.2-positive Advanced Solid Tumors
Dual-targeting CLDN18.2 and PD-L1 CAR-T for Patients with CLDN18.2-positive Advanced Solid Tumors
分数与星级只用于站内排序 —— 不代表疗效、安全性或个人适用性。
⚠ 该试验的登记信息已有 23 个月未更新， 页面上显示的「招募中」可能已经失效。联系研究中心之前，建议先到 ClinicalTrials.gov 核对登记原文的最新状态与联系方式。
这是一项 I 期注册临床试验，评估 CAR-T 细胞治疗晚期实体瘤的安全性、可行性及初步疗效。当前状态：招募中。计划入组 29 例。试验地点：中国 · 成都（共 1 个中心，其中中国 1 个）。登记号：NCT06084286。
不限性别 · ≥ 18 Years 且 ≤ 75 Years
纳入标准： 1. 男女不限，年龄18–75岁； 2. 病理/组织学确诊实体瘤（如晚期胃腺癌、胃食管结合部腺癌或胰腺腺癌），至少接受过一次标准全身治疗后疾病进展；或一线治疗后拒绝/无法耐受后续标准治疗； 3. CLDN18.2免疫组化检测显示肿瘤表达阳性细胞≥10%； 4. 研究者判断预期生存期>3个月； 5. 按RECIST 1.1标准至少有一个可测量病灶； 6. ECOG体能状态评分0或1分； 7. 有足够静脉通路用于白细胞单采，且无其他单采禁忌证； 8. 血常规、肾功能及肝功能基本正常； 9. 无其他严重疾病（自身免疫性疾病或任何免疫缺陷病）； 10. 有生育能力的女性在筛查前及细胞输注前须进行血清妊娠检测且结果阴性，并愿意在T细胞输注后至少12个月内采取有效可靠的避孕措施； 11. 男性须愿意在T细胞输注后至少12个月内采取有效可靠的避孕措施，且不得捐献精子； 12. 自愿参加研究，理解并签署知情同意书。 排除标准： 1. 妊娠期或哺乳期女性； 2. 活动期乙型或丙型肝炎，或HIV感染水平达到/超过正常值上限； 3. 任何未控制的活动性感染； 4. 有临床意义的甲状腺功能障碍； 5. 既往接受过CAR-T、TCR、TIL（肿瘤浸润淋巴细胞）等细胞治疗； 6. 对免疫治疗或相关药物（如细胞因子及预处理方案中的环磷酰胺、氟达拉滨）过敏； 7. 未治疗的中枢神经系统（CNS）转移、软脑膜疾病或脊髓压迫； 8. 研究者认为参加试验可能危及患者健康的有临床意义心脏病； 9. 入组前6个月内发生不稳定肺栓塞、深静脉血栓或其他重大动静脉血栓栓塞事件； 10. 活动性自身免疫性疾病、自身免疫性疾病史，或其他需要免疫抑制治疗的疾病； 11. 白细胞单采前4周内接受过大手术或遭受损伤，或研究期间计划接受大手术； 12. 筛查前5年内除目标肿瘤外患有第二种恶性肿瘤； 13. 存在不稳定/活动性溃疡或消化道出血； 14. 患有影响签署书面知情同意或遵守研究程序的疾病，或不愿/不能遵守研究要求； 15. 有消化道出血史或倾向； 16. 主要研究者认为不适合参加本研究。
Inclusion Criteria: 1. Male or female, Age 18-75 years old; 2. Patients with pathologically/histologically confirmed diagnosis of solid tumors (such as advanced gastric adenocarcinoma or gastroesophageal junction adenocarcinoma and pancreatic adenocarcinoma) have received at least once systemic standard treatment and disease progressed; or refused/ cannot tolerate the subsequential standard treatment after the first line treatment; 3. Must have CLDN18.2-positive tumor expression ≥10% as determined by the CLDN18.2 IHC assay; 4. Estimated life expectancy \> 3 months (according to investigator's judgement); 5. At least 1 measurable lesion per RECIST 1.1; 6. The Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1; 7. Sufficient venous access for leukapheresis collection and no other contraindications to leukapheresis; 8. Patients should have reasonable CBC counts, renal and hepatic functions; 9. No other serious diseases (autoimmune diseases or any immune deficiency disease); 10. Women of childbearing age must undergo a serum pregnancy test with negative results before screening and infusion and be willing to use effective and reliable method of contraception for at least 12-months after T-cell infusion; 11. Men must be willing to use effective and reliable method of contraception and are not allowed to donate sperm for at least 12-months after T-cell infusion; 12. Voluntarily participate in the research, understand and sign the informed consent. Exclusion Criteria: 1. Pregnant or lactating women; 2. Patient with hepatitis B or C active period, HIV infection ≥ the upper limit of the normal level; 3. Any uncontrolled active infection; 4. Patients who have clinically significant thyroid dysfunction; 5. Patients who have received prior cellular therapy such as CAR T, TCR, tumor-infiltrating lymphocytes; 6. Patients who are allergic to immunotherapy or any associated drugs, such as cytokines and the preconditioning regimen (cyclophosphamide, fludarabine); 7. Patients with untreated central nervous system (CNS) metastatic disease, leptomeningeal disease, or cord compression; 8. Patients have clinical significant cardiac conditions that researchers believe that participating in this clinical trial may endanger the health of the patients; 9. Unstable pulmonary embolism, deep venous embolism or other major arterial/venous thromboembolic events occurred within 6 months before enrollment; 10. Patients with active autoimmune diseases, history of autoimmune diseases or other diseases in need of immunosuppressive therapy; 11. Patients with major surgery or injury less than 4 weeks prior to leukapheresis or plan to have major surgery during the research period; 12. Patients with second malignancies in addition to targeted malignancies within 5 years before screening; 13. Patients with unstable/active ulcer or digestive tract bleeding; 14. Patient suffering from diseases that affect the signing of written informed consent or compliance with research procedures; or are unwilling or unable to comply with research requirements; 15. Patients who have a history or a tendency for digestive tract bleeding; 16. Patients who are inappropriate to participate in this research as considered by PI.
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) · Safety evaluation. AEs will be recorded and evaluated by CTCAE 5.0. · 28 days；Dose-limiting toxicity (DLT) · Tolerability evaluation. DLT will be assessed by CTCAE 5.0. · 28 days；Recommended phase II dose (RP2D) · Efficacy dose. · Approximately 18 months
次要终点：Objective Remission Rate (ORR)；Progression-Free Survival (PFS)；Duration of Control Rate (DCR)；Duration of Response (DOR)；Overall-Survival (OS)；CAR-T cell numbers；Anti-CAR antibody production；CAR-T cell phenotype
CLDN18.2和PD-L1双靶向CAR-T 细胞。
以上邮箱 / 电话是登记库里的申办方联系方式（+86，中国），通常不直达某家医院。中国中心的联系方式请以医院或登记平台最新公示为准。
Claudin 18.2（CLDN18.2）是一种位于上皮与内皮紧密连接处的整合膜蛋白，在多种实体瘤中高表达，尤其常见于胃癌和胰腺癌。本研究将在CLDN18.2阳性晚期实体瘤患者中评估CLDN18.2/PD-L1双靶向CAR-T 细胞。
Claudin18.2(CLDN18.2) is a kind of integrin membrane protein in the tight junction between epithelium and endothelium, which is highly expressed in many solid tumors, especially in gastric cancer and pancreatic cancer. The CLDN18.2/PD-L1 dual-targeting CAR-T will be investigated in patients with CLDN18.2-positive advance solid tumors.
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