Clinical Study of a Novel Humanized CD70-Targeted CAR-T Cell Incorporating TLR2 for Advanced Renal Cell Carcinoma Therapy

NCT07113977 | Not Yet Recruiting Early Phase 1

• 1 other identifier: TJ-IRB202502144
• Study Type: interventional
• Target: 30
• Locations: 0 countries
• Sites: N/A

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.

Conditions

Advanced Renal Cell Carcinoma

Keywords

CD70; CAR-T; Advanced renal cell carcinoma

Outcome Measures

Primary Outcomes (3)

• 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

Secondary Outcomes (3)

• 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

Study Arms (1)

Experimental Arm

EXPERIMENTAL

Biological: CAR-T(CD70)

Interventions

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.

Experimental Arm

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• \. Voluntary participation with written informed consent provided by the patient or legally authorized representative;
• Age 18-75 years (inclusive) at the time of consent, regardless of sex;
• 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;
• Histopathologically confirmed advanced RCC per WHO 2016 classification, with at least one measurable lesion evaluable by CT or MRI;
• CD70 positivity in tumor tissue confirmed by immunohistochemistry (IHC);
• 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;
• 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;
• Performance status: ECOG score 0-3;
• Life expectancy \>3 months;
• Willingness to comply with leukapheresis, medical assessments, and follow-up visits.

You may not qualify if:

• Pregnant or lactating women;
• Uncontrolled fungal, bacterial, Treponema pallidum, viral, or other infections;
• Active hepatitis: HBV DNA \>500 IU/mL. Positive HCV RNA (confirmed by repeat testing);
• HIV infection, known acquired immunodeficiency syndrome (AIDS), or syphilis infection;
• Prior gene therapy of any form;
• History of severe allergic reactions to biologics (including antibiotics), antibodies, cytokines, or other macromolecular agents;
• Clinically significant CNS disorders: epilepsy, paresis, aphasia, stroke, severe traumatic brain injury, dementia, Parkinson's disease, cerebellar disorders, organic brain syndrome;
• Uncontrolled psychiatric illness;
• Substance abuse/addiction;
• 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.

Sponsors & Collaborators

• Wei Guan: lead

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: July 24, 2025
• First Posted: August 11, 2025
• Study Start: August 15, 2025
• Primary Completion (Estimated): August 31, 2028
• Study Completion (Estimated): December 31, 2028
• Last Updated: August 11, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will not share