肿瘤细胞治疗研究
英文原题：Dual-Target CAR-NK Cells Directed Against MSLN, EGFR, or HER2 in Advanced NSCLC
这是一项 I/II 期注册临床试验，评估 NK 细胞治疗非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 48 例。试验地点：中国 · 深圳（共 1 个中心，其中中国 1 个）。登记号：NCT07467863。
不限性别 · ≥ 18 Years 且 ≤ 75 Years
纳入标准： * 经组织学或细胞学确诊的NSCLC，不可切除的IIIB/IIIC期或IV期；接受标准治疗（包括含铂化疗，以及适用时的免疫检查点抑制剂）期间或之后影像学显示疾病进展。 * 至少有1个符合RECIST v1.1标准的可测量病灶。 * 有存档肿瘤组织，或愿意接受新鲜活检，用于抗原检测。 * 筛查时肿瘤至少共表达以下两种抗原：MSLN、EGFR、HER2/ERBB2。示例阈值：每种所需抗原在≥50%的肿瘤细胞中IHC染色≥2+（或达到相当的RNA表达阈值）。 * ECOG体能状态评分0–1分。 * 按方案实验室标准，血液、肝和肾功能充分。 * 预期寿命≥12周。 * 有生育能力者妊娠试验阴性，并同意在方案规定期间采取有效避孕措施。 * 能够理解研究内容并愿意签署书面知情同意书。 排除标准： * 活动性、未控制的中枢神经系统（CNS）转移。既往经治疗且稳定的CNS疾病患者，如临床情况稳定且未使用大剂量皮质类固醇，可能符合入组条件。 * 过去3个月内接受过基因修饰细胞治疗（如CAR-T、CAR-NK、TCR-T），或研究者认为会增加严重毒性风险的既往治疗。 * 既往治疗中发生过严重细胞因子释放综合征（CRS）或免疫效应细胞相关神经毒性综合征（ICANS）。 * 有临床意义的间质性肺病或需全身类固醇治疗的肺炎，或未控制且会干扰毒性监测的肺部合并症。
Inclusion Criteria: * Histologically or cytologically confirmed NSCLC that is unresectable Stage IIIB/IIIC or Stage IV, with radiographic progression on or after standard-of-care therapy (including platinum-based chemotherapy and immune checkpoint inhibitor when appropriate). * At least one measurable lesion per RECIST v1.1. * Archival tumor tissue available (or willingness to undergo a fresh biopsy) for antigen testing. * Tumor co-expression of at least two of the following antigens at screening: MSLN, EGFR, HER2/ERBB2. Example thresholds: IHC ≥2+ in ≥50% of tumor cells for each required antigen (or an equivalent RNA expression threshold). * ECOG performance status 0-1. * Adequate organ function (hematologic, hepatic, renal) as defined by protocol laboratory limits. * Life expectancy ≥12 weeks. * Negative pregnancy test for individuals of childbearing potential; agreement to use effective contraception for the study-defined period. * Ability to understand and willingness to sign written informed consent. Exclusion Criteria: * Active, uncontrolled central nervous system (CNS) metastases. Participants with previously treated/stable CNS disease may be eligible if clinically stable and off high-dose corticosteroids. * Prior gene-modified cellular therapy (e.g., CAR-T, CAR-NK, TCR-T) within 3 months, or any prior therapy that in the investigator's judgment increases risk of severe toxicity. * History of severe cytokine release syndrome (CRS) or immune effector cell-associated neurotoxicity syndrome (ICANS) with prior therapies. * Clinically significant interstitial lung disease or pneumonitis requiring systemic steroids, or uncontrolled pulmonary comorbidity that would confound toxicity monitoring.
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；Objective response rate (ORR) · 6 months
次要终点：Duration of response (DOR) per RECIST v1.1.；Progression-free survival (PFS).；Overall survival (OS)
肿瘤共表达MSLN和EGFR并达到筛查阈值的受试者接受淋巴细胞清除治疗，随后按分配剂量输注EB-DuoNK-MSLN/EGFR。
肿瘤共表达MSLN和HER2/ERBB2的受试者接受淋巴细胞清除治疗，随后按分配剂量输注EB-DuoNK-MSLN/HER2。
肿瘤共表达EGFR和HER2/ERBB2的受试者接受淋巴细胞清除治疗，随后按分配剂量输注EB-DuoNK-EGFR/HER2。
这项分为两部分的生物标志物指导Ⅰ/Ⅱ期研究，评估现货型双靶点CAR-NK细胞治疗晚期或转移性非小细胞肺癌（NSCLC）的安全性、可行性及初步抗肿瘤活性。患者肿瘤需共表达以下至少两种抗原：间皮素（MSLN）、EGFR和HER2/ERBB2。 患者将先接受淋巴细胞清除化疗，随后输注与其肿瘤抗原特征相匹配的CAR-NK产品。研究将依据中期数据评估，选择最合适的构建体进入扩展阶段。
This is a two-part, biomarker-guided Phase 1/2 study evaluating the safety, feasibility, and preliminary anti-tumor activity of off-the-shelf dual-target CAR-NK cells in participants with advanced or metastatic NSCLC whose tumors co-express at least two of the following antigens: Mesothelin (MSLN), EGFR, and HER2/ERBB2. Participants will receive lymphodepleting chemotherapy followed by infusion of the CAR-NK product matched to their tumor antigen profile. A data-driven interim assessment will be used to select the most suitable construct for expansion.
MEMBER ACCOUNT
登录成功会直接打开下一页。
