Dual-target CD70 and CAIX CAR-NK therapy for advanced clear cell kidney cancer

Is this trial a fit for you?

A plain-English reading of the study's rules. Only the study team can confirm whether you qualify.

What this trial studies

Adults with advanced or metastatic clear cell renal cell carcinoma receive lymphodepletion with fludarabine and cyclophosphamide followed by an infusion (with an optional second dose on Day 15) of allogeneic, cord blood–derived NK cells engineered with a dual CAR against CD70 and CAIX, membrane-bound IL-15, and an inducible caspase-9 safety switch. A phase 1 dose-escalation will define a recommended dose and characterize hepatobiliary safety, followed by a biomarker-guided expansion analyzing CD70-high, CAIX-high, and dual-high subgroups. All participants remain in a single treatment arm but are prospectively analyzed by tumor biomarker status, and central testing of archival or fresh tumor tissue is required. Biomarker-defined activity signals will inform whether future development prioritizes CD70, CAIX, or continued dual-targeting.

Why it matters

Who can join: the full rules

Inclusion Criteria:

* Written informed consent and willingness to comply with protocol procedures.
* Age \>= 18 years at the time of consent.
* Histologically confirmed unresectable or metastatic clear cell RCC, or RCC with a clear-cell component, with radiographic progression after standard therapy.
* Prior exposure to at least one PD-1 / PD-L1-based regimen and at least one VEGF-pathway targeted regimen, or documented intolerance / unsuitability for available standard systemic options.
* At least one measurable lesion by RECIST 1.1.
* Available archival tumor tissue or willingness to undergo fresh biopsy for central biomarker testing; protocoldefined tumor positivity for CD70 and/or CAIX is required. Dual-positive cases are preferred for the biomarkerexpansion portion.
* ECOG performance status 0-1.
* Adequate marrow, liver, cardiac, pulmonary, and renal function as defined by the protocol (for example, ANC, platelets, bilirubin, AST/ALT, creatinine clearance, oxygen saturation, and left ventricular function within protocoldefined limits).
* Life expectancy of at least 12 weeks.
* Negative pregnancy test for participants of childbearing potential and agreement to highly effective contraception during protocol-defined risk windows.
* Previously treated brain metastases are allowed if clinically stable and off escalating corticosteroids for at least 14 days before lymphodepletion.

Exclusion Criteria:

* Active, untreated, or symptomatic central nervous system metastases, leptomeningeal disease, or uncontrolled seizure disorder.
* Prior gene-modified cellular therapy (including prior CAR-T, CAR-NK, CAR-NKT, or TCR-engineered therapy) within the protocol-defined washout window.
* Prior allogeneic stem cell transplant or solid organ transplant with ongoing clinically significant immunosuppression.
* Active autoimmune disease requiring systemic immunosuppressive treatment; physiologic replacement doses are permitted.
* Active uncontrolled infection, including uncontrolled hepatitis B, hepatitis C, HIV, tuberculosis, or sepsis.
* Clinically significant hepatobiliary disease that could increase risk from CAIX-directed therapy, such as active cholangitis, primary sclerosing cholangitis, biliary obstruction, Child-Pugh B/C cirrhosis, or prior hepatic venoocclusive disease.
* Clinically significant cardiovascular disease (for example, unstable angina, recent myocardial infarction, uncontrolled arrhythmia, or clinically meaningful heart failure).
* Systemic corticosteroid use greater than 10 mg prednisone equivalent daily within 7 days before lymphodepletion, unless required as physiologic replacement.
* Pregnancy or breastfeeding.
* Another active invasive malignancy requiring systemic treatment, except for protocol-defined low-risk exceptions.
* Known hypersensitivity to fludarabine, cyclophosphamide, or a critical study-product excipient.

Where it's running

• Peking University Shenzhen Hospital
  Shenzhen, Guangdong, China Recruiting

Study contacts

• Study coordinator: shan S Lu, Phd
• Email: Seni-Lu@beijing-biotech.com
• Phone: +86 13076790030

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How to take part

1. Review the eligibility criteria above with your treating physician.
2. Check the official listing on ClinicalTrials.gov for the latest contact details and recruitment status.
3. Contact the study coordinator or principal investigator to ask for pre-screening. Pre-screening is free and never obligates you to enroll.