肿瘤细胞治疗研究
英文原题：Adaptive Phase 1/2 Study of Dual-Target CAR-NK Cells in Relapsed/Refractory Small Cell Lung Cancer (SCLC)
这是一项 I/II 期注册临床试验，评估 NK 细胞治疗小细胞肺癌的安全性、可行性及初步疗效。当前状态：招募中。计划入组 60 例。试验地点：中国 · 深圳（共 1 个中心，其中中国 1 个）。登记号：NCT07480213。
不限性别 · ≥ 18 Years 且 ≤ 75 Years
纳入标准： • 签署知情同意时年龄18～75岁。 • 组织学或细胞学确诊为转移性、广泛期或不可切除的小细胞肺癌（SCLC），且至少接受过1种全身治疗方案后复发或难治（除非有禁忌证，既往治疗须包含含铂方案）。 • 根据RECIST 1.1至少有1个可测量病灶。 • ECOG体能状态评分0～1分。 • 器官功能（血液学、肾脏、肝脏和心脏）符合方案规定；例如：ANC≥1.0×10⁹/L、血小板≥75×10⁹/L、肌酐清除率≥50 mL/min、AST/ALT≤ULN的3倍、总胆红素≤ULN的1.5倍。 • 预期生存期≥12周。 • 有可用于抗原分析（DLL3、CD56/NCAM1、GD2）的肿瘤组织（存档或新鲜样本）。 • 有生育能力者妊娠试验阴性；同意在方案规定期限内采取有效避孕措施。 排除标准： • 存在活动性或未控制的中枢神经系统（CNS）转移或软脑膜疾病（按方案规定，已治疗且稳定的CNS转移可能允许）。 • 过去6个月内接受过CAR-T、CAR-NK或其他基因修饰细胞治疗；或既往接受过针对试验靶抗原的治疗，且可能干扰安全性／疗效评估。 • 过去6个月内接受过异基因造血干细胞移植，或存在活动性移植物抗宿主病。 • 存在未控制的活动性感染，包括未控制的HIV、伴病毒血症的活动性乙型或丙型肝炎，或活动性结核。 • 存在有临床意义的心血管疾病，例如近6个月内发生心肌梗死、未控制的心律失常或左心室射血分数<45%。 • 患有需要全身免疫抑制治疗的活动性自身免疫性疾病；长期使用泼尼松等效剂量>10 mg/日的全身性糖皮质激素（生理替代治疗除外）。 • 合并需要积极治疗的恶性肿瘤（某些非黑色素瘤皮肤癌或原位癌可能例外）。 • 妊娠或哺乳期。 • 研究者认为会导致参加研究不安全或影响依从性的任何情况。
Inclusion Criteria: * Age 18 to 75 years at the time of consent. * Histologically or cytologically confirmed small cell lung cancer (SCLC) that is metastatic, extensive-stage, or unresectable, and relapsed or refractory after at least 1 prior systemic regimen (must include a platinum-based regimen unless contraindicated). * At least one measurable lesion per RECIST v1.1. * ECOG performance status 0 to 1. * Adequate organ function (hematologic, renal, hepatic, and cardiac) as defined in the protocol (examples: ANC \>= 1.0 x10\^9/L, platelets \>= 75 x10\^9/L, creatinine clearance \>= 50 mL/min, AST/ALT \<= 3 x ULN, total bilirubin \<= 1.5 x ULN). * Life expectancy \>= 12 weeks. * Tumor tissue available (archival or fresh) for antigen profiling (DLL3, CD56/NCAM1, GD2). * Negative pregnancy test for persons of childbearing potential; agreement to use effective contraception for the protocol-defined duration. Exclusion Criteria: * Active or uncontrolled CNS metastases or leptomeningeal disease (treated/stable CNS metastases may be allowed per protocol). * Prior treatment with CAR-T, CAR-NK, or other gene-modified cellular therapy within 6 months (or any prior therapy directed against the investigational target antigens if it would confound safety/efficacy assessment). * Allogeneic hematopoietic stem cell transplant within 6 months or active graft-versus-host disease. * Active uncontrolled infection, including uncontrolled HIV, active hepatitis B or C with viremia, or active tuberculosis. * Clinically significant cardiovascular disease (e.g., recent myocardial infarction within 6 months, uncontrolled arrhythmia, LVEF \< 45%). * Active autoimmune disease requiring systemic immunosuppression; chronic systemic corticosteroid use \> 10 mg/day prednisone equivalent (unless for physiologic replacement). * Concurrent malignancy requiring active treatment (exceptions may apply for certain non-melanoma skin cancers or in situ cancers). * Pregnant or breastfeeding. * Any condition that, in the investigator's opinion, would make participation unsafe or interfere with compliance.
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) · 28 Days；Maximum tolerated dose (MTD) · 12 months
次要终点：Objective response rate (ORR)；Progression-free survival (PFS)；Overall survival (OS)
淋巴细胞清除化疗后，给予靶向DLL3和CD56（NCAM1）的异基因双靶点CAR-NK细胞。
淋巴细胞清除化疗后，给予靶向DLL3和GD2的异基因双靶点CAR-NK细胞。
淋巴细胞清除化疗后，给予靶向CD56（NCAM1）和GD2的异基因双靶点CAR-NK细胞。
这是一项开放标签、多中心、适应性Ⅰ/Ⅱ期临床试验，旨在评估异基因双靶点CAR-NK细胞产品用于复发或难治性小细胞肺癌（SCLC）成人患者的安全性、可行性和初步抗肿瘤活性。剂量递增阶段将评估3种候选双靶点构建体（DLL3/CD56、DLL3/GD2和CD56/GD2）；预设的中期评估将选出最适宜的构建体，在推荐的Ⅱ期剂量（RP2D）下进入扩展队列。
This study is an open-label, multi-center, adaptive Phase 1/2 trial evaluating the safety, feasibility, and preliminary antitumor activity of allogeneic dual-target CAR-NK cell products in adults with relapsed or refractory small cell lung cancer (SCLC). Three candidate dual-target constructs (DLL3/CD56, DLL3/GD2, and CD56/GD2) will be assessed during dose escalation; a pre-specified interim assessment will select the most suitable construct to proceed into an expansion cohort at the recommended Phase 2 dose (RP2D).
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