An Open-Label, Multicenter, Randomized Phase II Study to Evaluate the Efficacy and Safety of Personalized Dendritic Cell Vaccine ZSNeo-DC1.1 in Combination With Temozolomide as Adjuvant Therapy in Patients With Newly Diagnosed Glioblastoma After Surgery and Concurrent Chemoradiotherapy
Overview
- Phase
- Phase 2
- Status
- Not yet recruiting
- Sponsor
- ZSky Biotech Inc
- Enrollment
- 78
- Primary Endpoint
- PFS
Overview
Brief Summary
This is a multicenter, open-label, randomized Phase II clinical study designed to evaluate the efficacy and safety of a personalized dendritic cell (DC) vaccine, ZSNeo-DC1.1, in combination with temozolomide (TMZ) as adjuvant therapy in patients with newly diagnosed glioblastoma (GBM).
Eligible patients with histologically confirmed, IDH1/IDH2 wild-type newly diagnosed glioblastoma who have undergone tumor debulking surgery followed by standard concurrent chemoradiotherapy will be enrolled. After confirmation of tumor neoantigens and eligibility, patients will be randomized in a 1:1 ratio to receive either ZSNeo-DC1.1 in combination with TMZ or TMZ alone.
The primary objective is to evaluate progression-free survival (PFS) as assessed by an Independent Radiological Review Committee (IRRC) according to RANO 2.0 criteria. Secondary objectives include overall survival (OS), survival rates, tumor response outcomes, and safety. Exploratory objectives include assessment of antigen-specific T-cell immune responses induced by ZSNeo-DC1.1.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to 75 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Participants must meet all the following criteria to be eligible:
- •Inclusion Criteria
- •Age 18 to 75 years, inclusive
- •Histologically confirmed newly diagnosed glioblastoma (WHO grade IV)
- •Molecular diagnosis of IDH1/IDH2 wild-type
- •Completion of tumor debulking surgery followed by standard concurrent chemoradiotherapy
- •Karnofsky Performance Status (KPS) score of 50 to 100
- •Adequate hematologic, hepatic, renal, and coagulation function
- •Availability of sufficient tumor tissue and blood samples for neoantigen identification
- •Adequate venous access for PBMC collection
Exclusion Criteria
- •Exclusion Criteria:
- •Subjects meeting any of the following criteria are ineligible:
- •Not suitable for standard temozolomide-based chemoradiotherapy
- •Prior participation in another interventional clinical trial within 4 weeks before randomization
- •Prior implantation of carmustine wafers within 6 months
- •Known hypersensitivity to temozolomide or dacarbazine
- •Active autoimmune disease or requirement for systemic immunosuppressive therapy
- •Active infection including HIV, active hepatitis B or C, or syphilis
- •Use of systemic immunosuppressive therapy within 30 days before randomization
- •Uncontrolled cardiovascular, metabolic, or systemic disease
Arms & Interventions
Experimental
Personalized dendritic cell vaccine ZSNneo-DC1.1 in combination with temozolomide.
Intervention: Personalized Dendritic Cell Vaccine ZSNeo-DC1.1 (Biological)
Experimental
Personalized dendritic cell vaccine ZSNneo-DC1.1 in combination with temozolomide.
Intervention: Temozolomide (TMZ) (Drug)
Control
Standard adjuvant temozolomide chemotherapy alone
Intervention: Temozolomide (TMZ) (Drug)
Outcomes
Primary Outcomes
PFS
Time Frame: From randomization until disease progression or death, whichever occurs first，assessed up to 24 months
Progression-free survival assessed by an Independent Radiological Review Committee according to RANO 2.0 criteria
Secondary Outcomes
- OS(From randomization until death from any cause，assessed up to 36 months)
- Overall Survival Rates(12 months, 18 months, and 24 months)
- Investigator-Assessed Progression-Free Survival(From randomization until disease progression or death，assessed up to 24 months)
- Disease Control Rate (DCR)(During treatment period)
- Best Overall Response (BOR)(During treatment period)
- 6. Clinical Benefit Rate (CBR)(During treatment period)
- Safety and Tolerability(From first dose until 30 days after last dose，assessed up to 24 months)