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
Phase 1/2 study evaluates the safety, feasibility, and preliminary antitumor activity of allogeneic dual-target CD70/CAIX CAR-NK cells after fludarabine/cyclophosphamide lymphodepletion in adults with advanced or metastatic clear cell RCC that has progressed after standard therapy. The study is designed to determine a recommended dose and schedule, characterize hepatobiliary safety, and explore whether CD70-high, CAIX-high, or dual-high tumors derive the greatest benefit. Biomarker-defined activity signals will be used to guide whether later development should prioritize CD70, CAIX/CA9, or continued dual-targeting.
• 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.