A Clinical Trial of P134 Cells in Recurrent Glioblastoma

ConditionRecurrent Glioblastoma IDH Wildtype

Trial statusRecruiting

Trial phasePhase 1, Phase 2

Trial typeInterventional

Biological sexAll

Age18-70

SponsorTasly Pharmaceutical Group Co., Ltd

About this trial

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.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

Voluntary written informed consent.

18-70 years of age (inclusive), male or female.

Recurrent or progressive glioblastoma, histopathologically or molecularly diagnosed consistent with grade 4 glioblastoma (IDH wild-type) (refer to WHO Classification of Central Nervous System Tumors, 5th Edition, 2021).

Positive CD44 or CD133 antigen expression in tumor tissue confirmed by IHC, defined as ≥1% of tumor cells showing positive CD44 or CD133 IHC staining, regardless of intensity (applicable only in Phase II dose expansion study).

Disqualifiers

Highly allergic constitution or history of severe allergy, or allergy to related cell products

Receipt of biologic anti-tumor therapy (including monoclonal or bispecific antibody-targeted therapy, immune checkpoint inhibitor therapy, etc.) within 6 weeks prior to PBMC collection; receipt of radiotherapy or surgery within 4 weeks prior to PBMC collection (excluding placement of vascular access devices; a 1-week washout period is acceptable for diagnostic biopsy surgeries); receipt of chemotherapy, hormone therapy (excluding hormone replacement therapy), or non-specific immunomodulatory therapy (such as interleukins, interferons, thymosin, cyclophosphamide, methotrexate, tumor necrosis factor, etc.) within 2 weeks prior to PBMC collection; receipt of traditional Chinese medicine therapy with a clear anticancer indication within 1 week prior to PBMC collection.

The adverse reactions caused by previous anti-tumor treatment have not recovered to ≤ Grade 1 as evaluated by NCI CTCAE v6.0 (except alopecia, skin pigmentation, leukoplakia, etc. which are assessed as having no safety risk).

Tumor metastasis to the brainstem or spinal cord.

Trial design

Design model

Single group

Treatments tested in this trial

P134 cell injection
Biological/Vaccine
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.

Treatment groups

26 Participants

are divided into 1 treatment group

Group A: P134 cellExperimental treatment 1 intervention

Trial outcomes

Primary outcomes

Dose 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.

Secondary outcomes

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

Other outcomes

Cytokinetics

The number of CAR-positive (CAR+) cells in cerebrospinal fluid (CSF) measured by flow cytometry, expressed as cells per milliliter (cells/mL).

Time frame

From within 24 hours before the first CAR-T cell infusion through Day 28 after the last infusion, an average duration of five months

Cytokinetics

The copy number of CAR genes in the cerebrospinal fluid (CSF) of participants.

Time frame

From within 24 hours before the first CAR-T cell infusion through Day 28 after the last infusion, an average duration of five months

Immunogenicity

The incidence of patients with positive serum anti-CAR molecular antibodies

Time frame

From within 24 hours before the first CAR-T cell infusion through Day 28 after the last infusion, an average duration of five months.

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

Tasly Pharmaceutical Group Co., Ltd

Lead sponsor

Source ClinicalTrials.gov

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