肿瘤细胞治疗研究
英文原题：Target-Selected CAR-NK Cells (CD30, CD5, or Mesothelin) for Relapsed/Refractory B2 Thymoma or Thymic Carcinoma
这是一项 I/II 期注册临床试验，评估细胞治疗用于相关疾病的安全性、可行性及初步疗效。当前状态：招募中。计划入组 36 例。试验地点：中国 · 深圳（共 1 个中心，其中中国 1 个）。登记号：NCT07598955。
不限性别 · ≥ 18 Years 且 ≤ 75 Years
纳入标准： * 知情同意时年龄18–75岁； * 组织学确诊为B2型胸腺瘤或胸腺癌，且不可切除、转移或复发； * 至少接受过一线全身治疗后复发/难治（胸腺癌患者适用时须包括含铂方案），或无标准根治性治疗选择； * 中心实验室检测至少一种抗原阳性：CD30、CD5或间皮素；队列分配根据预设算法确定优势靶点，并考虑制备可行性/产品可及性； * 按RECIST v1.1有可测量疾病（如无法测量，则可纳入可评估疾病，具体待明确）； * ECOG体能状态0–1（扩展阶段研究者可酌情允许0–2）； * 器官功能充分：ANC≥1.0×10⁹/L、血小板≥75×10⁹/L、血红蛋白≥8 g/dL（允许输血）、AST/ALT≤ULN的3倍（肝受累时≤5倍）、总胆红素≤ULN的1.5倍（Gilbert综合征除外）、肌酐清除率≥50 mL/min； * 有生育能力者妊娠试验阴性并同意有效避孕； * 能够理解并签署知情同意书。 排除标准： * 存在需要立即治疗的活动性CNS恶性肿瘤受累； * 90天内接受过基因修饰细胞治疗（如CAR-T、CAR-NK），或既往细胞治疗相关≥2级毒性未缓解； * 未控制感染（包括活动性结核、未控制乙肝或丙肝）或已知未控制HIV感染； * 淋巴细胞清除前14天内有需全身免疫抑制治疗的有临床意义自身免疫病（如泼尼松等效剂量>10 mg/日），稳定的内分泌替代治疗除外； * 既往异体造血干细胞移植且存在活动性GVHD或仍接受免疫抑制治疗； * 有显著心血管疾病（如NYHA Ⅲ/Ⅳ级心衰、近期心肌梗死）、未控制心律失常或研究者认为会增加风险的QTc延长； * 妊娠或哺乳； * 21天内同时参加使用试验性抗癌药物的其他干预性试验（须满足洗脱期）； * 研究者认为会妨碍安全参加研究或结果解释的其他情况。
Inclusion Criteria: * Age 18 to 75 years at the time of consent. * Histologically confirmed B2 thymoma or thymic carcinoma that is unresectable, metastatic, or recurrent. * Relapsed or refractory after at least 1 prior systemic therapy (including a platinum-based regimen for thymic carcinoma when appropriate) or no standard curative option available. * Tumor antigen positivity for at least one of the following by central laboratory assessment: CD30, CD5, or mesothelin. Cohort assignment is based on the dominant target (pre-specified algorithm) and feasibility of manufacturing/availability. * Measurable disease per RECIST v1.1 (or evaluable disease if measurable disease is not feasible; to be specified). * ECOG performance status 0-1 (0-2 may be permitted in expansion at investigator discretion). * Adequate organ function: ANC ≥ 1.0 x 10\^9/L, platelets ≥ 75 x 10\^9/L, hemoglobin ≥ 8 g/dL (transfusions allowed), AST/ALT ≤ 3 x ULN (≤ 5 x ULN with liver involvement), total bilirubin ≤ 1.5 x ULN (except Gilbert's), creatinine clearance ≥ 50 mL/min. * Negative pregnancy test for participants of childbearing potential; agreement to use effective contraception. * Ability to understand and sign informed consent. Exclusion Criteria: * Active central nervous system involvement by malignancy requiring immediate therapy. * Prior gene-modified cellular therapy (e.g., CAR-T, CAR-NK) within 90 days or unresolved ≥Grade 2 toxicity from prior cellular therapy. * Uncontrolled infection, including active tuberculosis, or uncontrolled hepatitis B or C infection; known uncontrolled HIV infection. * Clinically significant autoimmune disease requiring systemic immunosuppression (e.g., \>10 mg/day prednisone equivalent) within 14 days of conditioning, except for stable endocrine replacement. * Prior allogeneic hematopoietic stem cell transplant with active graft-versus-host disease or ongoing immunosuppression. * Significant cardiovascular disease (e.g., NYHA class III/IV heart failure, recent myocardial infarction), uncontrolled arrhythmia, or QTc prolongation felt to increase risk. * Pregnancy or breastfeeding. * Concurrent participation in another interventional trial with an investigational anticancer agent within 21 days (washout required). * Any condition that, in the investigator's judgment, would interfere with safe participation or interpretation of results.
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：Incidence of Dose-Limiting Toxicities (DLTs) · DLTs as defined in protocol, assessed during the DLT window after the first CAR-NK infusion. Includes severe infusion-related toxicity, Grade \>=3 organ toxicity attributable to CAR-NK cells, severe CRS or neurotoxicity, and treatment-related death. · 28 Days；Recommended Phase 2 Dose · Determined separately for each cohort based on DLTs, overall safety, and pharmacodynamic data · 28 Days
次要终点：Objective Response Rate；Disease Control Rate
接受淋巴细胞清除化疗：环磷酰胺联合氟达拉滨（第−5至−3天），随后第0天输注CAR-NK。Ⅱ期若未发生≥3级治疗相关毒性且有可用产品，研究者可酌情在第7天再次输注。
接受淋巴细胞清除化疗：环磷酰胺联合氟达拉滨（第−5至−3天），随后第0天输注CAR-NK。Ⅱ期若未发生≥3级治疗相关毒性且有可用产品，研究者可酌情在第7天再次输注。
接受淋巴细胞清除化疗：环磷酰胺联合氟达拉滨（第−5至−3天），随后第0天输注CAR-NK。Ⅱ期若未发生≥3级治疗相关毒性且有可用产品，研究者可酌情在第7天再次输注。
本Ⅰ/Ⅱ期研究评估靶点选择性嵌合抗原受体自然杀伤（CAR-NK）细胞治疗成人复发或难治性B2型胸腺瘤或胸腺癌的安全性、耐受性和初步疗效。受试者接受集中肿瘤抗原检测（CD30、CD5和间皮素）；根据优势且具有临床可靶向性的抗原表达谱，分配至三个平行队列之一：CD30-CAR-NK、CD5-CAR-NK或间皮素-CAR-NK。所有队列均采用相同淋巴细胞清除预处理方案，随后输注CAR-NK细胞（可输注一次或多次）。
This Phase 1/2 study evaluates the safety, tolerability, and preliminary efficacy of target-selected CAR-natural killer (CAR-NK) cells in adults with relapsed or refractory B2 thymoma or thymic carcinoma. Participants undergo centralized tumor antigen assessment (CD30, CD5, and mesothelin). Based on the dominant and clinically actionable antigen expression profile, each participant is assigned to one of three parallel cohorts (CD30-CAR-NK, CD5-CAR-NK, or mesothelin-CAR-NK). All cohorts use the same lymphodepleting conditioning regimen followed by CAR-NK infusion(s).
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