A Clinical Study to Evaluate the Safety and Efficacy of Allogeneic CD70 CAR-T Therapy in Patients With Unresectable or Metastatic Clear Cell Renal Cell Carcinoma
CLEAR CAR-T cell injection (ET-970) is an engineered CD70-targeting allogeneic Chimeric Antigen Receptor T-Cell (CAR-T cell). This is a multi-center, single-arm, open-label, early exploratory clinical study. The objective of this study is to evaluate the safety and preliminary efficacy of ET-970 in unresectable or metastatic clear cell renal cell carcinoma.
• Age 18-75 years (inclusive), any gender. 2.Confirmed by histopathology and/or cytology as unresectable or metastatic clear cell renal cell carcinoma; 3.Local progression or metastasis after receiving at least second line therapy \[including at least one immune checkpoint inhibitor (ICI) and at least one vascular endothelial growth factor tyrosine kinase inhibitor (VEGF TKI)\]; 4.Willing to undergo tumor tissue sample collection or provide previous tumor tissue samples for CD70 expression level testing; 5.Positive CD70 expression by immunohistochemical (IHC) staining of tumor tissue (percentage of positive cells ≥ 10%); 6.At least one measurable lesion according to RECIST v1.1 criteria. 7.Karnofsky Performance Status (KPS) ≥ 70%. 8.Organ function must meet the following criteria:
⁃ Complete blood count (no G-CSF within 1 week prior to blood count testing. or no pegylated G-CSF within 2 weeks prior to blood count testing): Absolute neutrophil count (ANC) ≥ 1.0×10⁹/L. platelet count (PLT) ≥ 100×10⁹/L. hemoglobin ≥ 80 g/L (excluding bone marrow suppression caused by lymphoma involvement of the bone marrow).
⁃ Coagulation function: International normalized ratio (INR) ≤ 1.5×ULN, and activated partial thromboplastin time (APTT) ≤ 1.5×ULN.
⁃ Liver function: Serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3×ULN (if with liver metastasis, AST and ALT ≤ 5×ULN). total bilirubin ≤ 1.5×ULN.
⁃ Renal function: Serum creatinine ≤ 1.5×ULN or creatinine clearance (Cockcroft-Gault formula) ≥ 60 mL/min.
⁃ Cardiac function: Left ventricular ejection fraction (LVEF) on echocardiography (ECHO) ≥ 50%, no pericardial effusion. no clinically significant abnormalities on 12-lead electrocardiogram (ECG).
⁃ Pulmonary function: End-blood oxygen saturation ≥ 92% while breathing room air without supplemental oxygen. no clinically significant pleural effusion.
• Subjects and/or their partners of childbearing potential agree to use effective contraceptive measures throughout the entire treatment period and for 52 weeks after treatment, and during this period they must not donate eggs/sperm for assisted reproduction; Female participants of childbearing potential (women who have undergone sterilization surgery or have been postmenopausal for ≥12 months are not considered to have childbearing potential) must present a negative pregnancy test at screening and agree to use effective contraception throughout the study period.
⁃ Willing to comply with all study procedures and voluntarily participate in this study and sign the informed consent form (ICF).