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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Experimental Arm | Experimental |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| CAR-T(CD70) | Biological | 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 administered intratumorally under CT guidance at the pre-specified dose. Following treatment, the efficacy and safety of CD70-directed CAR-T-cell therapy will be comprehensively assessed through clinical symptom evaluations, quality-of-life questionnaires, biomarker analyses, laboratory tests, imaging studies, adverse-event monitoring, and long-term follow-up. |
| Measure | Description | Time Frame |
|---|---|---|
| Immune Effector Cell-Associated Neurotoxicity Syndrome(ICANS) | To assess the number and severity of ICANS after treatment according to the ASTCT criteria | in 6 months |
| Cytokine Release Syndrome(CRS) | To assess the number and severity of CRS after treatment according to the ASTCT criteria | in 6 months |
| Objective response rate (ORR) | Objective response rate (ORR) will be assessed by imaging at 1 month, 6 months, and 1 year post-CAR-T infusion. | 1 month, 6 months, and 1 year |
| Measure | Description | Time Frame |
|---|---|---|
| Progression-Free Survival(PFS) | The time from the start of treatment to disease progression, up to a maximum of 36 months. | |
| Overall Survival(OS) | The time from the start of treatment to death, up to a maximum of 36 months. |
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Inclusion Criteria:
1. 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:
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;
Exclusion Criteria:
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.
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| Adverse Events | Number of participants with treatment-related adverse events as assessed by CTCAE v4.0 | in six months |