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 Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
12
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
Beijing Tiantan Hospital, Capital Medical University
Beijing, Beijing Municipality, China
RECRUITINGAE and SAE
Evaluating the incidence rates of Adverse Events and Serious Adverse Events
Time frame: 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.
Time frame: 2 months
Assessment of ORR (Objective Response Rate)
According toRANO2.0, to assess the proportion of subjects achieving complete remission (CR) or partial remission (PR).
Time frame: 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)
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 2 years
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