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B7-H3 is expressed at low levels in normal tissues but overexpressed in various tumor tissues. The ubiquitous expression of B7-H3 in tumors of different grades is a key feature for brain gliomas. The immunohistochemistry study showed that B7-H3 is abundantly expressed on both glioma (especially high-grade glioma) cells and tumor-associated endothelial cells. For GBM, the expression of B7-H3 is intensely positive, especially on tumor cells and vascular endothelial cells, which makes B7-H3 a potential immunotherapeutic target.
γδ T cells recognize tumor cells without being restricted by MHC molecules, and thus can be used in allogeneic therapy without the risk of causing graft-versus-host disease.
This study is an open-label, single-arm, dose-escalation and dose-expansion clinical study aimed at evaluating the safety and efficacy of allogeneic B7-H3 CAR γδT in patients with malignant glioma.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Patients with R/R HGG | Experimental |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Allogenic B7-H3 CAR-γδT cell(QH104) | Biological | Dose escalation (3+3) : dose 1 (1 × 10^7 CAR+cells) , dose 2 (3 × 10^7 CAR+cells), dose 3 (6× 10^7 CAR+cells), once every 4 weeks via an Ommaya reservoir or intrathecal administration. Dose expansion 1: dose of RP2D, once every 4 weeks via an Ommaya reservoir or intrathecal administration. Dose expansion 2: 3 × 10^7 CAR+cells, every two weeks for three consecutive months, then changed to once every 4 weeks via an Ommaya reservoir or intrathecal administration. |
| Measure | Description | Time Frame |
|---|---|---|
| Phase 1: Incidence of Adverse Events (AEs) | AE is defined as any adverse medical event from the date of the cell infusion to 12 months after B7-H3 CAR-γδT cells infusion. Among them, cytokine release syndrome (CRS) and immune cell-associated neurotoxicity syndrome (ICANS) were graded according to American Society for Transplantation and Cellular Therapy (ASTCT) criteria, graft-versus-host disease (GVHD) according to criteria defined by the Mount Sinai Acute GVHD International Consortium. Other AEs were graded according to common terminology criteria for adverse events (CTCAE) v5.0. | 12 months |
| Phase 1:Incidence of Dose-Limiting Toxicities (DLTs) | DLT was defined as B7-H3 CAR-γδT cells-related events with onset within first 28 days following infusion | 28 days after the first dose of B7-H3 CAR-γδT cells |
| Phase 1:Maximum tolerated dose (MTD) | 28 days after the first dose of B7-H3 CAR-γδT cells | |
| Phase 1: Recommended phase 2 dose (RP2D) | 28 days after the first dose of B7-H3 CAR-γδT cells |
| Measure | Description | Time Frame |
|---|---|---|
| Pharmacokinetics: copy number of B7-H3 CAR-γδT cells in cerebrospinal fluid(CSF) | 28 days after the first dose of B7-H3 CAR-γδT cells | |
| Pharmacodynamics: Peak level of cytokines in CSF | 28 days after the first dose of B7-H3 CAR-γδT cells |
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Inclusion Criteria:
Exclusion Criteria:
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Dushu Lake Hospital Affiliated to Soochow University | Recruiting | Suzhou | Jiangsu | 215125 | China |
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| Phase 2: Overall survival (OS) | 6 months, 9 months and 12 months |
| Phase 2: Progression Free Survival (PFS) | 6 months |
| Disease Control Rate (DCR) | 6 months |