Clinical Study of a Novel Humanized CD70-Targeted CAR-T Cell Incorporating TLR2 for Advanced Renal Cell Carcinoma Therapy
试验速览
- 阶段
- 早期 1 期
- 状态
- 尚未招募
- 发起方
- 入组人数
- 30
- 主要终点
- Objective response rate (ORR)
研究概览
简要总结
In this clinical study, participants with advanced renal cell carcinoma will receive a novel humanized CD70-targeted CAR-T-cell product that incorporates the TLR2 co-stimulatory domain. Peripheral blood mononuclear cells will be collected from each subject, genetically modified to express the CAR construct, and expanded ex vivo; after passing multiple quality-control assays, the CAR-T cells will be infused at the pre-specified dose. Post-infusion, the efficacy and safety of CD70-directed CAR-T-cell therapy will be systematically evaluated using clinical symptom assessments, quality-of-life questionnaires, biomarker analyses, laboratory tests, imaging studies, adverse-event monitoring, and long-term follow-up.
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
- •Voluntary participation with written informed consent provided by the patient or legally authorized representative;
- •2.Age 18-75 years (inclusive) at the time of consent, regardless of sex;
- •3.Advanced-stage renal cell carcinoma (RCC) with no curative treatment options, who have received ≥1 prior line of therapy and meet one or more of the following:
- •Recurrence after first-line or later-line treatment(s).
- •Progression or persistent progression following prior therapy;
- •4.Histopathologically confirmed advanced RCC per WHO 2016 classification, with at least one measurable lesion evaluable by CT or MRI;
- •5.CD70 positivity in tumor tissue confirmed by immunohistochemistry (IHC);
- •6.Adequate organ function: Hepatic: ALT/AST <3× ULN and total bilirubin ≤34.2 μmol/L. Renal: Creatinine clearance (Cockcroft-Gault) ≥60 mL/min. Pulmonary: Oxygen saturation ≥95% with no active pulmonary infection. Cardiac: LVEF ≥50%, no significant pericardial effusion, and no clinically relevant ECG abnormalities;
- •7.Contraception: Women of childbearing potential must have a negative pregnancy test (urine/serum) at screening and agree to use effective contraception for ≥1 year post-infusion.
- •Men with partners of childbearing potential must use barrier contraception for ≥1 year post-infusion;
- •8.Performance status: ECOG score 0-3;
- •9.Life expectancy >3 months;
- •10.Willingness to comply with leukapheresis, medical assessments, and follow-up visits.
排除标准
- •1.Pregnant or lactating women;
- •2.Uncontrolled fungal, bacterial, Treponema pallidum, viral, or other infections;
- •3.Active hepatitis: HBV DNA >500 IU/mL. Positive HCV RNA (confirmed by repeat testing);
- •4.HIV infection, known acquired immunodeficiency syndrome (AIDS), or syphilis infection;
- •5.Prior gene therapy of any form;
- •6.History of severe allergic reactions to biologics (including antibiotics), antibodies, cytokines, or other macromolecular agents;
- •7.Clinically significant CNS disorders: epilepsy, paresis, aphasia, stroke, severe traumatic brain injury, dementia, Parkinson's disease, cerebellar disorders, organic brain syndrome;
- •8.Uncontrolled psychiatric illness;
- •9.Substance abuse/addiction;
- •10.Prohibited medications/treatments: Corticosteroids: ≥2 mg/kg prednisone (or equivalent >20 mg/day) within 2 weeks before leukapheresis.
- •Chemo/radiotherapy: Anti-tumor radiotherapy or salvage chemotherapy within 3 weeks before leukapheresis.
- •Immunosuppressants: Use within 4 weeks before leukapheresis. Other trials/major surgery: Participation in another clinical trial or major non-diagnostic surgery within 4 weeks before leukapheresis.
- •Specific agents: Alemtuzumab within 6 months, or clofarabine/cladribine within 3 months before leukapheresis.
研究组 & 干预措施
Experimental Arm
干预措施: CAR-T(CD70) (Biological)
结局指标
主要结局
Objective response rate (ORR)
时间窗: 1 month, 6 months, and 1 year
Objective response rate (ORR) will be assessed by imaging at 1 month, 6 months, and 1 year post-CAR-T infusion.
Cytokine Release Syndrome（CRS）
时间窗: in 6 months
To assess the number and severity of CRS after treatment according to the ASTCT criteria
Immune Effector Cell-Associated Neurotoxicity Syndrome（ICANS）
时间窗: in 6 months
To assess the number and severity of ICANS after treatment according to the ASTCT criteria
次要结局
- Adverse Events(in six months)
- Overall Survival（OS）(The time from the start of treatment to death, up to a maximum of 36 months.)
- Progression-Free Survival（PFS）(The time from the start of treatment to disease progression, up to a maximum of 36 months.)
研究者
Wei Guan
Professor
Tongji Hospital