This is an open-label, single-arm, dose-escalation and expansion Phase 1/2 clinical trial designed to evaluate the safety, tolerability and efficacy of P134 cells in patients with recurrent glioblastoma, to explore the maximum tolerated dose (MTD)and recommended Phase 2 dose (RP2D), and to characterize the cytokinetic profile of CAR-T cells in the cerebrospinal fluid of patients. Eligible participants are adults diagnosed with recurrent or progressive glioblastoma who are confirmed as grade 4 glioblastoma (IDH wild-type) by histopathology or molecular pathology. P134 cells are CD44/CD133 dual-targeting CAR-T cells developed by the research team led by Academician Jiang Tao and Professor Zhang Wei from the Beijing Neurosurgical Institute and the Department of Neurosurgery, Beijing Tiantan Hospital. This study is spearheaded by Professor Zhang Wei of the Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, China, with scientific oversight and guidance provided by Academician Jiang Tao of the Chinese Academy of Engineering.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
26
In Phase 1 dose-escalation study, P134 cell dosing and safety are evaluated using an accelerated titration initial dose followed by a "3+3" design. The starting dose is 1 × 10⁸ CAR⁺ T cells, administered intratumorally or intraventricularly via an Ommaya reservoir. Three dose levels are planned: Level 1: 1 × 10⁸ CAR⁺ T cells, Q2W. Level 2: 3 × 10⁸ CAR⁺ T cells, Q2W. Level 3: 5 × 10⁸ CAR⁺ T cells, Q2W. The Level 1 adopts accelerated titration, and the Level 2 and Level 3 adopt the "3+3" design. In Phase 2 dose expansion, one or two dose levels will be selected based on integrated safety, efficacy, and other relevant data. Up to 10 participants will be enrolled per dose level (including subjects from the dose-escalation study).Participants will be enrolled sequentially from the lower dose level to the higher dose level: enrollment at the lower dose level will be completed first, followed by enrollment at the higher dose level.
Beijing Tiantan Hospital, Capital Medical University
Beijing, China
RECRUITINGDose limiting toxicities (DLTs)
Proportion of participants with dose-limiting toxicities (DLTs) as assessed by CTCAE version 6.0 in the dose-escalation phase
Time frame: From the first dose up to Day 28 post-first dose
Adverse events (AEs)
Incidence and severity of adverse events (safety and tolerability) as assessed by CTCAE version 6.0 in the dose-escalation phase.
Time frame: Through study completion, an average of two and a half years
Maximum tolerated dose (MTD)
The highest dose level with less than 33% of participants experiencing dose-limiting toxicities (DLTs) as assessed by CTCAE version 6.0 in the dose-escalation phase.
Time frame: From the first dose up to Day 28 after the first dose.
Recommended Phase 2 Dose (RP2D)
The optimal dose level identified based on the safety data (incidence of adverse events, dose-limiting toxicities \[DLTs\]), preliminary efficacy data , and pharmacodynamic data in the dose-escalation phase.
Time frame: From study enrollment to Day 28 after the last dose of participants in the dose-escalation phase
Objective Response Rate (ORR)
the proportion of participants who achieve a complete response (CR) or partial response (PR) as assessed by RANO 2.0 criteria.
Time frame: Through study completion, an average of two and a half years
Disease Control Rate (DCR)
the proportion of participants who achieve a complete response (CR), partial response (PR), or stable disease (SD) as assessed by RANO 2.0 criteria.
Time frame: Through study completion, an average of two and a half years
Progression-Free Survival (PFS)
The time from study enrollment to the first occurrence of disease progression (as assessed by RANO 2.0) or death from any cause, whichever occurs first
Time frame: Through study completion, an average of two and a half years
Duration of Response (DOR)
The time from the first documentation of a complete response (CR) or partial response (PR) (as assessed by RANO 2.0) to the first documentation of objective tumor progression or death from any cause, whichever occurs first.
Time frame: Through study completion, an average of two and a half years
Time to Response (TTR)
the time from study enrollment to the first documentation of a complete response (CR) or partial response (PR) as assessed by RANO 2.0
Time frame: Through study completion, an average of two and a half years
1-year OS Rate
the proportion of participants who are still alive 12 months after study enrollment
Time frame: From study enrollment up to 12 months after study enrollment
Overall Survival
The time from study enrollment to death from any cause
Time frame: Through study completion, an average of two and a half years
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