A Prospective Study on Super Hi-TCR-T Cells Targeting Nectin4/NKG2DL/TROP2/B7H3/GPC3/FAP for the Treatment of Refractory/Relapsed Advanced Liver Cancer and Other Solid Tumors
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 30
- 试验地点
- 1
- 主要终点
- progression-free survival
研究概览
简要总结
This study is a prospective, single-arm, open, single-center clinical trial initiated by the investigator. The principal investigators are professors Shen Feng and Zhang Xiaofeng from The Third Affiliated Hospital of Navy Military Medical University (Shanghai Eastern Hepatobiliary Surgery Hospital).
Primary Objectives:
- To evaluate the safety and tolerability of super Hi-TCR-T cells targeting Nectin4/NKG2DL/TROP2/B7H3/GPC3/FAP in the treatment of refractory/recurrent advanced hepatocellular carcinoma (HCC) and other solid tumors.
- To assess the efficacy of super Hi-TCR-T cells targeting Nectin4/NKG2DL/TROP2/B7H3/GPC3/FAP in the treatment of refractory/recurrent advanced HCC and other solid tumors, focusing on progression-free survival (PFS).
Secondary Objectives:
- To evaluate the efficacy of super Hi-TCR-T cells targeting Nectin4/NKG2DL/TROP2/B7H3/GPC3/FAP in the treatment of refractory/recurrent advanced HCC and other solid tumors at 1, 3, 6, and 12 months, assessing disease control rate (DCR: CR+PR+SD), time to progression (TTP), and overall survival (OS).
- To observe and assess the quality of life (QOL score) of patients receiving super Hi-TCR-T cell therapy targeting Nectin4/NKG2DL/TROP2/B7H3/GPC3/FAP for refractory/recurrent advanced HCC and other solid tumors.
Exploratory Objectives:
- To evaluate the relationship between the in vivo expansion and persistence of super Hi-TCR-T cells targeting Nectin4/NKG2DL/TROP2/B7H3/GPC3/FAP and disease progression.
- To explore potential predictive biomarkers. Thirty patients are planned to be recruited for this study. The subjects were advanced HCC patients who had failed second-line therapy or could not tolerate therapy. The expression levels of Nectin4, NKG2DL, TROP2, B7H3, GPC3 and FAP were detected by immunohistochemistry in the pathologic tissues of the primary and metastatic sites. Meanwhile, 20ml peripheral blood was extracted to evaluate the quality of T cells (in vitro proliferation activity and lentiviral transduction efficiency). Patients with positive expression rates of at least 2 targets (excluding FAP) >10% and qualified T cell quality could be considered for inclusion.
Peripheral blood lymphocytes were collected and Hi-TCR-T cells targeting three targets (including FAP) were prepared. After pretreatment with fludarabine + cyclophosphamide chemotherapy (FC regimen), the prepared Hi-TCR-T cells were transfused back, in which the dose of Hi-TCR-T cells at each target was 3.0x106 cells/kg body weight (the dose was the extended therapeutic dose obtained in the previous clinical trial), and the drug was administered by peripheral intravenous infusion. To improve efficacy, Hi-TCR-T cell retransfusion can be prepared by increasing the cell dose of the target or changing the combination of the target as the disease progresses and evaluated by a multidisciplinary team (MDT).
Safety and efficacy evaluation and exploratory studies were conducted after reinfusion of Hi-TCR-T cells from screening multiple targets:
- Safety assessment: at baseline, 4, 7, 10, 2, 3, 4, 8, 12, 16, 20, 6, 9 and 12 months after cell therapy;
- Effectiveness evaluation: at baseline, 4, 12, 6, 9, 12, 24, and 36 months after cell therapy. Safety assessment: At baseline, 4, 7, 10, 2, 3, 4, 8, 12, 16, 20, 6, 9, and 12 months after cell therapy;
- Exploratory study: 20ml peripheral blood was collected from patients at baseline, 7 days, 2 weeks, 4 weeks, 8 weeks, 12 weeks, 16 weeks, 20 weeks, 6 months, 9 months, 12 months after cell therapy, to explore the relationship between the proliferation and survival time of Hi-TCR-T cells in vivo and the changes of disease and peripheral blood cytokines.
The start time of the study was defined as the date the first patient was enrolled; The end time of the study was defined as 12 months after the end of medication for the final patient, or all patients died, or all patients had lost follow-up or withdrawn consent (whichever occurred first). The planned recruitment period is 12-18 months.
详细描述
- Stage 1: Preparatory period (expected 3-6 months) Ethical review and approval: Submit the trial application to the relevant ethics committee, including detailed design of the patient's informed consent, to ensure compliance with ethical requirements and obtain approval.
Trial protocol registration: Clinical trials are registered on the clinical trial registration platform.
Test site and equipment preparation: Ensure that test facilities and personnel training are in place.
Preparation for recruitment: publicity work for patient recruitment was carried out. 2. Second stage: Patient recruitment and treatment period (expected 12-18 months)
Patient recruitment and screening: According to inclusion and exclusion criteria, suitable patients were screened and informed consent was signed.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- 未提供
排除标准
- 未提供
研究组 & 干预措施
Hi-TCR-T Cell Therapy Group
干预措施: Super Hi-TCR-T cells (Biological)
结局指标
主要结局
progression-free survival
时间窗: From the date of enrollment of each patient, the end point was 12 months after the end of the patient's medication, or the patient died (whichever occurred first).
In treated subjects, the time from first recording to tumor progression (based on RECIST 1.1 and mRECIST) or death from any cause.
Adverse event
时间窗: From the date of enrollment of each patient, the end point was 12 months after the end of the patient's medication, or the patient died, or the patient was lost to follow-up or withdrew consent (whichever occurred first).
Adverse medical events that occur after a clinical trial subject is accepted into the trial, but are not necessarily causally related to the treatment. All adverse events that occur during the trial must be faithfully recorded on the Adverse Event sheet.
次要结局
- time to progress(From the date of enrollment of each patient, the end point was 12 months after the end of the patient's medication.)
- Disease Control Rate(From the date of enrollment of each patient, the end point was 12 months after the end of the patient's medication, or the patient died (whichever occurred first).)
- Overall survival(From the date of enrollment of each patient, the end point was 12 months after the end of the patient's medication, or the patient died (whichever occurred first).)
- duration of disease control(From the date of enrollment of each patient, the end point was 12 months after the end of the patient's medication, or the patient died (whichever occurred first).)
研究者
Xiao-Feng Zhang
The Vice President of the Clinical Research Institute
Eastern Hepatobiliary Surgery Hospital