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

An Open-Label, Multicenter, Phase 1/2 Study of Allogeneic Dual-target CD70/CAIX (CA9) Chimeric Antigen Receptor Natural Killer Cells in Adults With Advanced or Metastatic Clear Cell Renal Cell Carcinoma

This trial will try an off-the-shelf CAR-NK cell treatment that targets CD70 and CAIX for adults with advanced or metastatic clear cell kidney cancer who have progressed after standard therapies.

Quick facts

• Phase: Phase1; Phase2
• Study type: Interventional
• Enrollment: 36 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Beijing Biotech (Industry-sponsored)
• Drugs / interventions: CAR-T, cyclophosphamide, fludarabine, prednisone
• Locations: 1 site (Shenzhen, Guangdong)
• Trial ID: NCT07551349 on ClinicalTrials.gov

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.

Who should consider this trial

Good fit: Adults (≥18) with unresectable or metastatic clear cell RCC who have progressed after PD‑1/PD‑L1 and VEGF-pathway therapies, have ECOG 0–1, measurable disease, adequate organ function, and available tumor tissue for CD70/CAIX testing.

Not a fit: Patients with non–clear-cell histology, poor performance status, significant organ dysfunction, or tumors negative for both CD70 and CAIX are unlikely to benefit from this intervention.

Why it matters

Potential benefit: If successful, it could provide a new off-the-shelf cellular therapy that shrinks tumors or controls disease in patients who no longer respond to checkpoint inhibitors and VEGF-targeted drugs.

How similar studies have performed: CD70-directed cell therapies have shown encouraging clinical signals in RCC while prior CAIX-targeted CAR approaches demonstrated activity but raised hepatobiliary safety concerns, making this dual-target CAR-NK approach novel and partly informed by earlier results.

Eligibility criteria

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 this trial is running

Shenzhen, Guangdong

• Peking University Shenzhen Hospital — Shenzhen, Guangdong, China (Recruiting)

Study contacts

• Study coordinator: shan S Lu, Phd

Conditions Advanced or Metastatic Clear Cell Renal Cell Carcinoma; RCC; kidney cancer; clear cell renal cell carcinoma