Advanced Renal Cell Carcinoma
Conditions
Keywords
CD70, CAR-T, Advanced renal cell carcinoma
Brief summary
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.
Interventions
BIOLOGICALCAR-T(CD70)
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.
Sponsors
Wei Guan
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
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: 1. Recurrence after first-line or later-line treatment(s). 2. 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.
Exclusion criteria
* 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Immune Effector Cell-Associated Neurotoxicity Syndrome（ICANS） | in 6 months | To assess the number and severity of ICANS after treatment according to the ASTCT criteria |
| Cytokine Release Syndrome（CRS） | in 6 months | To assess the number and severity of CRS after treatment according to the ASTCT criteria |
| Objective response rate (ORR) | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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. | — |
| Adverse Events | in six months | Number of participants with treatment-related adverse events as assessed by CTCAE v4.0 |
Outcome results
None listed