Safety and Efficacy Study for DC Vaccine in Recurrent or Progressive High-grade Gliomas

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.

Inclusion Criteria:

• Participants must meet all the following criteria to be eligible:

  1. Age from 18 to 75 years (including 18 and 75 years old).

  2. Subjects with histologically or cytologically confirmed WHO grade III-IV gliomas experiencing recurrence or progression after standard treatment.

  3. 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.

  4. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 2.

  5. 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.

  6. 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.

  7. Relief of any acute, clinically significant treatment-related toxicities (excluding alopecia) to ≤ Grade 1 before the first treatment.

  8. Heart function: Stable hemodynamics, LVEF ≥ 50%.

  9. Adequate venous access for PBMC collection, with no contraindications.

  10. Non-surgically sterilized reproductive-age subjects must use contraception during the study and have a negative pregnancy test.

  11. Expected survival period > 3 months.

  12. Voluntary participation, signed informed consent.

  13. Based on health and lab assessments, the investigator sees favorable risk-benefit for the subject in the clinical trial.

  14. Subjects must consistently comply, actively participate in follow-up visits, and undergo regular testing and evaluation at the research center throughout the trial.

Exclusion Criteria:

• Subjects meeting any of the following criteria are ineligible:

  1. Recent participation in other drug trials, concurrent anti-tumor therapy (excluding allowed bridging therapy) within 4 weeks before initial treatment, had blood transfusions, EPO, G-CSF, or GM-CSF in the 14 days before peripheral blood mononuclear cell collection, or received live virus vaccinations within 28 days before the first treatment.

  2. Subjects who had camptothecin sustained-release agent implantation surgery within 6 months before the initial treatment.

  3. Active autoimmune diseases, prolonged use of immunosuppressive therapy, or known egg allergy.

  4. Positive for HIV or syphilis antibodies, or active hepatitis B or C.

  5. Recent systemic immunosuppressive treatment within 30 days before the initial treatment.

     Note: Short-term, systemic immunosuppressive treatment may be considered in consultation with the investigator and sponsor approval. The washout period and its duration before the initial treatment will be decided in consultation with the sponsor for these patients.

     Allowed: Inhaled glucocorticoids for COPD, salt corticosteroids (e.g., fludrocortisone) for orthostatic hypotension, and low-dose glucocorticoid supplements (≤10 mg/day prednisone or equivalent) for adrenal insufficiency.

  6. Exclusion: Severe vaccine allergy history, use of attenuated live vaccines within 28 days before initial treatment, or anticipated need within 6 months after the last dose of the investigational drug.

  7. Uncontrolled systemic diseases, including cardiovascular diseases, organ failure, diabetes, and poorly controlled hypertension.

  8. Unmanageable mental illness or significant medical history that may increase risks or interfere with results.

  9. Thrombotic events within the first 6 months before initial treatment, unless anticoagulation can be discontinued during the screening period.

  10. Irreversible electrolyte imbalances.

  11. Severe infection in the first month before initial treatment, poorly controlled infection, or requiring antibiotic treatment within the past week (excluding prophylactic use).

  12. Pregnant or lactating subjects.

  13. Factors judged by the investigator that may necessitate premature study termination, such as non-compliance, other severe diseases requiring concurrent treatment, severe laboratory abnormalities, or family/social factors affecting subject safety or data/sample collection.