This is an open-label, single-arm clinical study designed to evaluate the safety and preliminary efficacy of EphA2-targeted CAR-DC combined with CAR-T cell therapy in patients with non-small cell lung cancer.
Main purpose: To evaluate the safety of EphA2-targeted CAR-T cells in combination with CAR-DCs in patients with advanced non-small cell lung cancer during the dose-escalation phase. To determine the maximum tolerated dose of EphA2-targeted CAR-DCs when administered in combination with CAR-T cells. Secondary purpose: To assess the overall response rate (ORR), including complete response (CR) and partial response (PR), as well as overall survival (OS) and disease-free survival (DFS) in patients receiving the combination therapy. To evaluate the in vivo persistence, immunophenotype, and functional activity of CAR-T cells and CAR-DCs following infusion.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
18
Autologous T cells genetically modified to express a chimeric antigen receptor (CAR) targeting EphA2
Autologous dendritic cells (DCs) genetically modified to express a chimeric antigen receptor (CAR) targeting EphA2
Second Affiliated Hospital, School of Medicine, Zhejiang University
Hangzhou, Zhejiang, China
RECRUITINGSafety: Incidence and severity of adverse events
To evaluate adverse events occurring within the first three months following infusion of EphA2-targeted CAR- T cells and CAR-DCs. The assessment includes incidence and severity of treatment-related symptoms such as neurological toxicity, hematological abnormalities, infections, autoimmune reactions, and secondary malignancies.
Time frame: First 3 month post CAR-T cells and CAR-DCs infusion
Efficacy: Remission Rate
To evaluate the proportion of participants who achieve an objective tumor response, including complete remission (CR) and partial remission (PR)
Time frame: 3 months post CAR-T cells and CAR-DCs infusion
Progression-Free Survival
Time frame: Up to 24 months post CAR-T cells and CAR-DCs infusion
Overall Survival
Time frame: Up to 24 months post CAR-T cells and CAR-DCs infusion
Relapse Rate
Time frame: Up to 24 months post CAR-T cells and CAR-DCs infusion
Duration of Response
Time frame: Up to 24 months post CAR-T cells and CAR-DCs infusion
In Vivo Persistence of CAR-T cells and CAR-DCs and Cytokine Profile Monitoring
The copy number of CAR-T cells and CAR-DCs in PBMCs will be measured by qPCR to assess in vivo persistence. Serum cytokine levels, including IL-2, IL-4, IL-6, IFN-γ, TNF-α, IL-10, IL-12, and IL-17A, will be quantified by ELISA to evaluate immune activation following cell infusion.
Time frame: First 2 weeks post CAR-T cells and CAR-DCs infusion
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Objective Response Rate in Participants Receiving Different Doses of CAR-DCs
The proportion of participants in each CAR-DCs dose cohort (5x10\^6, 1x10\^7, 3x10\^7, and 9x10\^7 cells) who achieve an objective tumor response, including completeremission (CR) or partial remission (PR). All participants received a fixed dose of EphA2-targeted CAR-T cells (2x10\^6 cells/kg) following CAR-DCs infusion.
Time frame: Up to 24 months post CAR-T cells and CAR-DCs infusion
Incidence and Severity of Treatment-Related Adverse Events in Participants Receiving Different Doses of CAR-DCs
To evaluate adverse events occurring following infusion of EphA2-targeted CAR-DCs and CAR-T cells. Participants will receive CAR-DCs at one of four dose levels (5x10\^6, 1x1 0\^7, 3x10\^7, and 9x10\^7 cells), followed by a fixed dose of EphA2-targeted CAR-T cells(2x10\^6 cells/kg). The assessment includes the incidence and severity of treatment-related symptoms such as neurological toxicity, hematological abnormalities, infections, autoimmune reactions, and secondary malignancies.
Time frame: Up to 24 months post CAR-T cells and CAR-DCs infusion