A Phase I Clinical Study to Evaluate the Safety and Tolerability of Anti-Human CD70 T-Cell Injection in Subjects With Advanced/Metastatic Renal Cell Carcinoma
This is a single-arm, open-label, dose-escalating Phase 1 clinical study. It aims to evaluate the safety, tolerability and pharmacokinetic(PK) profiles of the investigational agent, and preliminarily assess its efficacy in subjects with advanced/metastatic renal cell carcinoma, and determine the recommended dose and infusion regimen for Phase 2 trials.
• Age 18 to 70 years (inclusive), regardless of gender;
• Life expectancy of more than 12 weeks;
• Eastern Cooperative Oncology Group Performance Status (ECOG PS) score of 0 to 1;
• Subjects with advanced/metastatic renal cell carcinoma (RCC):
‣ Histologically confirmed clear cell renal cell carcinoma (ccRCC), with an International Metastatic RCC Database Consortium (IMDC) risk stratification of intermediate or high risk as evaluated by the investigator;
⁃ Has at least one measurable lesion according to RECIST 1.1;
⁃ Tumor tissue samples must test positive for CD70 expression via immunohistochemistry (IHC);
⁃ Must have received at least one prior line of systemic therapy (must include at least: (1) immuno-oncology (IO) combination therapy: concomitant targeting of PD-1 and CTLA-4, or (2) an immune checkpoint inhibitor (PD-1/PD-L1 inhibitor) combined with a VEGF/VEGFR-targeted agent);
• Venous access required for apheresis can be established; hemoglobin ≥ 90 g/L, absolute neutrophil count (ANC) ≥ 1.5×10\^9/L, and platelet count ≥ 100× 10\^9/L, and the leukepheresis can be carried according to the judgement of investigators;
• Hepatic, renal, cardiac, and pulmonary functions must meet the following criteria:
‣ Creatinine clearance (CrCl) ≥ 50 mL/min (calculated by the Cockcroft-Gault formula);
⁃ Left ventricular ejection fraction (LVEF) \> 50%;
⁃ Baseline peripheral oxygen saturation \> 95%;
⁃ Total bilirubin ≤2 × upper limit of normal (ULN);
⁃ Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤2.5 × ULN;
• Voluntary participation in the clinical study: Must understand and be informed about this study, voluntarily sign the Informed Consent Form (ICF), and be willing to complete all study procedures.