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.

Study Overview

• Status: Recruiting
• Conditions: WHO Grade III Gliomas; WHO Grade IV Gliomas
• Intervention / Treatment: Biological: personalized dendritic cell injection ZSNeo-DC1.1

• Study Type: Interventional
• Enrollment (Estimated): 12
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Yang Zhang, Dr; Phone Number: 59976516 010; Email: zhangyang8025@yeah.net
• Study Contact Backup: Name: Xiaomin Ma; Phone Number: 82342973 0518; Email: xiaomin.ma@zskybio.com

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100071
      • Recruiting
      • Beijing Tiantan Hospital, Capital Medical University
      • Contact: Yang Zhang, Dr; Phone Number: 59976516 010; Email: zhangyang8025@yeah.net
      • Principal Investigator: Nan Ji, Dr
      • Sub-Investigator: Yang Zhang, Dr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment Sequence A	Biological: personalized dendritic cell injection ZSNeo-DC1.1; Sequence A: For the first 3 cycles, 1 week as a dosing cycle, the next 3 cycles, 3 weeks as a dosing cycle, a total of 6 dosing cycles Sequence B: For the first 3 cycles, 1 week as a dosing cycle, the next 3 cycles, 2 weeks as a dosing cycle, a total of 6 dosing cycles; Other Names: DC vaccine
Experimental: Treatment Sequence B	Biological: personalized dendritic cell injection ZSNeo-DC1.1; Sequence A: For the first 3 cycles, 1 week as a dosing cycle, the next 3 cycles, 3 weeks as a dosing cycle, a total of 6 dosing cycles Sequence B: For the first 3 cycles, 1 week as a dosing cycle, the next 3 cycles, 2 weeks as a dosing cycle, a total of 6 dosing cycles; Other Names: DC vaccine

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
AE and SAE	Evaluating the incidence rates of Adverse Events and Serious Adverse Events	Throughout the whole clinical trial, around 2 years.
DLT	Dose-limiting toxicity.Referencing the results of the exploratory clinical study of ZSNeo-DC1.1 injection, clinical trial outcomes of similar drugs, and the NCI CTCAE 5.0 toxicity assessment criteria to determine DLT. The observation period for DLT is set during the activation of the subject's anti-tumor immune response, from the first day of treatment until 21 days after the third injection.	2 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Assessment of ORR (Objective Response Rate)	According toRANO2.0, to assess the proportion of subjects achieving complete remission (CR) or partial remission (PR).	For Sequence A/B, ORR is measured both on Day57, and after, ORR is measured when every 8 weeks, until the date of disease progression or death, whichever came first, assessed up to 2 years.
Assessment of DCR (Disease Control Rate)	According to RANO2.0, to assess the proportion of subjects achieving complete remission (CR), partial remission (PR), and stable disease (SD)	For Sequence A/B, DCR is measured both on Day57, and after, ORR is measured when every 8 weeks, until the date of disease progression or death, whichever came first, assessed up to 2 years.
Assessment of CBR (Clinical Benefit Rate)	According to RANO2.0, to assess the proportion of subjects in each treatment group with the best overall therapeutic effect, defined as the sum of Complete Remission (CR), Partial Remission (PR), and Stable Disease (SD), lasting for at least 6 months.	For Sequence A/B, CBR is measured until the date of disease progression or death, whichever came first, assessed up to 2 years.
Assessment of PFS (Progression Free Survival)	According to RANO2.0, to assess the PFS of the patients.	For Sequence A/B, PFS is measured both on Day57, and after, PFS is measured when every 8 weeks), until the date of disease progression or death, whichever came first, assessed up to 2 years.
OS (Overall survival)	Time from enrollment to the dates of death from any cause or last follow up reported.	2 years

Collaborators and Investigators

• Sponsor: Beijing Tiantan Hospital
• Collaborators: ZhongSheng BioTech Inc.

Study record dates

Study Major Dates

• Study Start (Actual): February 2, 2024
• Primary Completion (Estimated): December 24, 2024
• Study Completion (Estimated): February 4, 2025

Study Registration Dates

• First Submitted: February 2, 2024
• First Submitted That Met QC Criteria: February 2, 2024
• First Posted (Actual): February 12, 2024

Study Record Updates

• Last Update Posted (Actual): March 5, 2024
• Last Update Submitted That Met QC Criteria: March 4, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Astrocytoma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Glioblastoma; Glioma; Physiological Effects of Drugs; Immunologic Factors; Vaccines
• Other Study ID Numbers: ZSKY2023-1002

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No