This study is a single-arm, open-label, dose-escalating + dose-expansion clinical study, aiming to evaluate the safety and efficacy of CD70-targeted CAR-T cell preparations, and to preliminarily observe the study drug in CD70-positive advanced malignant tumors. The pharmacokinetic characteristics of CAR-T cell preparations for the treatment of patients with CD70-positive advanced malignancies were obtained and the recommended dose and infusion schedule.
Age ≥18 years, regardless of gender;
Histologically or cytologically confirmed advanced/metastatic solid tumors (tumors with positive CD70 expression, confirmed histopathological ly with IHC 3+ score);
Failed or intolerant to standard second-line treatments (at least one of the following: tyrosine kinase inhibitors (TKIs), poly(ADP-ribose) polymerase inhibitors (PARPi), anti-angiogenic therapy; disease progression or inability to tolerate surgery, chemotherapy, radiotherapy, or targeted therapy);
Extranodal lesions with a long axis ≥10mm on CT scan;
Prior treatment with anti-CD70 therapies;
Active/symptomatic central nervous system (CNS) metastasis or meningeal metastasis: Subjects with treated brain metastases are eligible if treatment was completed ≥4 weeks prior to screening and there is no evidence of progression on imaging;
Participation in other interventional clinical trials within 3 months before cell infusion (for unapproved drugs, the last dose must be ≥3 months prior; for approved drugs, ≥5 half-lives prior to cell infusion);
Received chemotherapy or targeted therapy within 2 weeks prior to blood collection or within 5 half-lives of the drug (whichever is shorter);
Parallel
CD70-targeted CAR-T cells
Biological/VaccineAdministration method: intravenous infusion. Subjects will receive conditioning therapy by Fludarabine and Cyclophosphamide before cell infusion.
CD70-targeted CAR-T cells
Biological/VaccineAdministration method: intrapleural infusion. Subjects will receive conditioning therapy by Fludarabine and Cyclophosphamide before cell infusion.
CD70-targeted CAR-T cells
Biological/VaccineAdministration method: intraperitoneal infusion. Subjects will receive conditioning therapy by Fludarabine and Cyclophosphamide before cell infusion.
To evaluate the safety of CAR-T cell preparations in the treatment of CD70-positive advanced malignancies [Safety and Tolerability]
Incidence of adverse events during the study, evaluated per the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 and American Society for Transplantation and Cellular Therapy (ASTCT) criteria
Obtained the recommended dose and infusion regimen of CAR-T cells for the treatment of patients with CD70-positive advanced malignancies [Safety and Tolerability]
Dose-limiting toxicity after CD70 CAR-T cell infusion
Assessing disease control rates of CAR-T cell preparations in CD70-positive advanced malignancies [Effectiveness]
Disease control rate: The proportion of subjects who achieved CR, PR, SD after CAR-T infusion accounted for all treated subjects (Assessed based on RECIST criteria)，the minimum value is 0%，maximum value is 100%, and higher scores mean a better outcome.
To characterize the in-vivo cellular kinetics of CAR-T cells【pharmacokinetics】
Cmax: maximum observed level of circulating CAR-T cells in peripheral blood after infusion
To characterize the in-vivo cellular kinetics of CAR-T cells【pharmacokinetics】
To determine the time to maximum observed level of circulating CAR-T cells (Tmax)；To estimate AUC0-28d and AUC0-90d for circulating CAR-T cells
To assess the inflammatory response following CAR-T cell infusion
Serum levels of inflammation-related markers and cytokines, including but not limited to C-reactive protein (CRP), interleukin-6 (IL-6), and ferritin
Objective response rate (ORR) of CD70 CAR-T treatment in patients with CD70-positive advanced malignancies [Effectiveness]
Objective response rate includes：The proportion of subjects who achieved CR, PR after CAR-T infusion accounted for all treated subjects (Assessed based on RECIST criteria)，the minimum value is 0%，maximum value is 100%, and higher scores mean a better outcome.
Duration of Response (DOR) of CD70 CAR-T treatment in patients with CD70-positive advanced malignancies [Effectiveness]
DOR will be assessed from the first assessment of CR/PR/SD to the first assessment of recurrence or progression of the disease or death from any cause
Progress-free survival(PFS) of CD70 CAR-T treatment in patients with CD70-positive advanced malignancies [Effectiveness]
PFS will be assessed from the first CD70 CAR-T cell infusion to death from any cause or the first assessment of progression(Assessed based on RECIST criteria)
Overall survival(OS)of CD70 CAR-T treatment in patients with CD70-positive advanced malignancies [Effectiveness]
OS will be assessed from the first CD70 CAR-T cell infusion to death from any cause (Assessed by investigators based on IRECIST criteria)
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