肿瘤细胞治疗研究
英文原题：An Phase I Trial of a CAR T-cell Infusion C-CAR031 in Participants With GPC3+ Advanced/Metastatic Squamous Cell Lung Cancer
这是一项 I 期注册临床试验，评估细胞治疗用于肺癌的安全性、可行性及初步疗效。当前状态：招募中。计划入组 24 例。试验地点：中国 · 上海（共 1 个中心，其中中国 1 个）。登记号：NCT07444281。
不限性别 · ≥ 18 Years 且 ≤ 75 Years
纳入标准： • 组织学或细胞学确诊不可切除IIIB期、IIIC期或IV期肺鳞癌。 • 中心实验室免疫组化检测证实GPC3表达。 • 晚期/转移性肺鳞癌患者既往不超过3线系统治疗后疾病进展或不耐受。 • 至少有一个可测量靶病灶。 • 超声心动图测得左心室射血分数（LVEF）≥50%，且报告为无损害。 • 肺功能足够。 • 实验室检查结果符合研究要求。 • 有生育能力女性血清或尿液妊娠试验须阴性；未绝育男性和女性同意在C-CAR031输注后至少12个月内采取有效避孕措施，或直至PCR检测CAR-T低于检测下限（LLOD），以较晚者为准。 排除标准： • 已知存在驱动基因突变，且根据当地治疗指南建议接受靶向标准治疗。 • 已知对CAR-T产品或其辅料（包括二甲基亚砜〔DMSO〕）存在危及生命的过敏、超敏反应或不耐受。 • 禁忌使用淋巴细胞清除药物，包括氟达拉滨和/或环磷酰胺。 • 有脾切除术或器官移植史。 • 既往接受过任何CAR-T疗法或任何靶向GPC3的治疗。 • 存在未控制或伴发的肺部疾病。 • 有临床意义的腹水。 • 未控制的胸腔积液或心包积液，需反复引流。 • 癌症相关脊髓压迫、软脑膜疾病或脑转移。 • 在单采前方案规定的时间范围内接受过放疗、局部治疗、疫苗、输血或全身治疗。 • 有研究方案规定的活动性疾病或病症史，或当前存在此类情况。
Inclusion Criteria: * Histologically or cytologically confirmed unresectable Stage IIIB ,IIIC or IV squamous cell lung cancer * Confirmed to express GPC3, as assessed by immunohistochemistry at a central lab * Participants who have progressed or intolerant to no more than three lines of prior systemic therapies for advanced/metastatic squamous cell lung cancer * At least one measurable target lesion * The left ventricular ejection fraction (LVEF) measured by echocardiography ≥50% and reported as non-impaired. * Sufficient pulmonary function * The laboratory testing results meet the study requirements * Female participants of childbearing potential must test negative for pregnancy in serum or urine. Non-sterilized participants (males and females) agree to take effective contraceptive measures for at least 12 months and until CAR-T below lower limit of detection (LLOD) by PCR which occurs last after C-CAR031 infusion. Exclusion Criteria: * known to harbor a driver mutation for which targeted standard therapy is recommended in accordance with local treatment guidelines. * Known life-threatening allergies, hypersensitivity, or intolerance to the CAR-T product or its excipients, including dimethyl sulfoxide (DMSO) * Contraindication to lymphodepleting agents, including fludarabine and/or cyclophosphamide. * History of splenectomy or organ transplantation * Prior treatment with Any CAR-T therapy OR any therapy that is targeting GPC3 * Uncontrolled or intercurrent pulmonary disease * Clinically meaningful ascites * Uncontrolled pleural effusion or pericardial effusion requiring recurrent drainage procedures * Cancer-related spinal cord compression, leptomeningeal disease, or brain metastases * Received radiation therapy, local treatment, vaccine, blood transfusion, systemic treatment within certain period of apheresis required by study protocol * History of or with active diseases or conditions of that's defined in study protocol
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：AE/SAE/AESI, DLT · * To assess the safety and tolerability of C-CAR031 in participants
* To determine the RDE (Phase Ia) · From baseline to 28 days after treatment
次要终点：ORR (Objective Response Rate)；CK Parameter and Quantification of CAR copies/μg DNA of C-CAR031；Presence of RCL；DCR (Disease Control Rate)；DoR (Duration of Response)；DRR (Durable Response Rate)；TTR (Time to Response)；PFS (Progression-free Survival)
受试者接受剂量水平1：0.75 mpk C-CAR031输注。
受试者接受剂量水平2：1.5 mpk C-CAR031输注。
受试者接受剂量水平3：4.0 mpk C-CAR031输注。
这项单臂、开放标签、多中心I期研究将评估C-CAR031治疗GPC3阳性晚期/转移性肺鳞癌成人患者的安全性、耐受性、抗肿瘤活性、药代动力学（PK）/药效学（PD）、生物标志物及免疫原性。患者不适合根治性治疗，并在既往不超过3线系统治疗（包括免疫检查点抑制剂〔CPI〕和含铂双药化疗，可同时或序贯使用）后疾病进展或不耐受。
This single-arm, open-label, multicenter, Phase I study will evaluate the safety, tolerability, anti-tumor activity, pharmacokinetics (PK)/pharmacodynamics (PD), biomarker, and immunogenicity of C-CAR031 in adult participants with GPC3+ advanced/metastatic squamous cell lung cancer, who are not amenable to curative therapy and have progressed or are intolerant to no more than 3 lines of prior systemic treatment including immune checkpoint inhibitors (CPIs) and platinum-based doublet chemotherapy, concurrently or sequentially.
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