Phase I Clinical Trial of Personalized Dendritic Cell Injection ZSNeo-DC1.1 in the Treatment of Recurrent or Progressive High-grade Glioma
This is a single-center, open-label, multi-dose phase I clinical trial evaluating the safety, tolerability, and preliminary efficacy of ZSNeo-DC1.1, a personalized dendritic cell injection, in subjects with recurrent or progressive WHO grade III-IV gliomas post-standard treatment. The subjects are adult GBM patients who have undergone surgical resection for recurrence. After the completion of reoperation, subjects will receive autologous DC vaccine treatments as scheduled. The autologous genetic-modification-free DC cells will be loaded with multiple tumor neoantigen peptides and administered (i.h) to subjects. After 3 injections, the investigator will review subject's tolerance and compliance. The DLT observation period spans from the initial injection to 21 days after the third injection, aligning with the activation of anti-tumor immune response. About 15 subjects will be enrolled. The study utilizes a fixed dose of 1×10\^7 cells per injection and employs two immunization schedules A or B. The trial is conducted in two stages: Dose Confirmation Stage: Enrollment of six subjects with recurrent or progressive gliomas following standard treatment. Each subject receives six subcutaneous injections of ZSNeo-DC1.1. Utilization of a standard 3+3 design for fixed dose confirmation and exploration of immunization schedules A and B. Dose Expansion Stage: Enrollment of at least six subjects with recurrent or progressive gliomas post-standard treatment. Administration of six subcutaneous injections of ZSNeo-DC1.1 to each subject, further investigating the safety and preliminary efficacy of ZSNeo-DC1.1 injection.
• Participants must meet all the following criteria to be eligible:
‣ Age from 18 to 75 years (including 18 and 75 years old).
⁃ Subjects with histologically or cytologically confirmed WHO grade III-IV gliomas experiencing recurrence or progression after standard treatment.
⁃ Bridging therapy is allowed during the preparatory period after sample collection, with discontinuation at least 7 days or 5 drug half-lives (whichever is longer) before the initial treatment.
⁃ Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 2.
⁃ Laboratory test results defining satisfactory hematological and organ function:
‣ Platelets (PLT) ≥ 90 × 10\^9/L; Absolute Neutrophil Count (ANC) ≥ 1.5 × 10\^9/L; Haemoglobin (HGB) ≥ 90 g/L; Serum Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) ≤ 2.5× ULN; Total Bilirubin (TBIL) ≤ 2.5 × ULN; Albumin (ALB) ≥ 3 g/dl; Creatinine clearance rate (CrCl) ≥ 45 mL/minute or Serum Creatinine ≤ 1.5 ×ULN; International Normalized Ratio (INR), Activated Partial Thromboplastin Time (APTT) ≤ 1.5 × ULN; Lipase ≤ 1.5 × ULN; Amylase ≤ 1.5 × ULN; Alkaline Phosphatase (ALP) ≤ 2.5 × ULN.
⁃ Adequate tumor and blood samples for NGS gene sequencing can be obtained through tumor reduction surgery or biopsy. Peripheral blood mononuclear cell function is normal.
⁃ Relief of any acute, clinically significant treatment-related toxicities (excluding alopecia) to ≤ Grade 1 before the first treatment.
⁃ Heart function: Stable hemodynamics, LVEF ≥ 50%.
⁃ Adequate venous access for PBMC collection, with no contraindications.
‣ Non-surgically sterilized reproductive-age subjects must use contraception during the study and have a negative pregnancy test.
‣ Expected survival period \> 3 months.
‣ Voluntary participation, signed informed consent.
‣ Based on health and lab assessments, the investigator sees favorable risk-benefit for the subject in the clinical trial.
‣ Subjects must consistently comply, actively participate in follow-up visits, and undergo regular testing and evaluation at the research center throughout the trial.