Dual-target CD70/CAIX CAR-NK Cells for Advanced Clear Cell Renal Cell Carcinoma

Korábbi kezelés

• 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.
• 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.
• Systemic corticosteroid use greater than 10 mg prednisone equivalent daily within 7 days before lymphodepletion, unless required as physiologic replacement.

Más betegség

• Active, untreated, or symptomatic central nervous system metastases, leptomeningeal disease, or uncontrolled seizure disorder.
• 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 cardiovascular disease (for example, unstable angina, recent myocardial infarction, uncontrolled arrhythmia, or clinically meaningful heart failure).
• 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.

Egyéb

• Pregnancy or breastfeeding.

• 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.