Clinical Study on the Treatment of Malignant Brain Glioma by QH104 Cell Injection

ConditionsBrain Gliomas High-Grade Gliomas GBM

Trial statusRecruiting

Trial phasePhase 1, Phase 2

Trial typeInterventional

Biological sexAll

Age18-70

SponsorDushu Lake Hospital Affiliated to Soochow University

About this trial

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.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

1)Age 18-70 years old (both ends included), both male and female;

2)At least one evaluable lesion, with previous biopsy or histopathological confirmation of high-grade glioma (WHO grade 3-4), and after comprehensive treatment, imaging examination indicates continued progression or recurrence;

3) The pathological tissues removed by surgery can be used for immunohistochemical detection of target proteins (paraffin sections should be within half a year), and the expression of B7-H3 is positive;

4) KPS ≥ 60 points;

Disqualifiers

1)Pregnant and lactating women;

2)Those with organ failure:Heart: Class III and IV;Liver: up to grade C of the Child-Turcotte Liver -Function Classification;Kidney: chronic kidney disease stage 4 or above; renal insufficiency stage III or above;Lungs: symptoms of severe respiratory failure with involvement of other organs;Brain: central nervous system abnormalities or impaired consciousness;

3)patients with combined second tumors;

4)patients with active hepatitis B or C virus, HIV infection, or other untreated active infection;

Trial design

Design model

Sequential

Treatments tested in this trial

Allogenic B7-H3 CAR-γδT cell(QH104)
Biological/Vaccine
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.

Treatment groups

25 Participants

are divided into 1 treatment group

Group A: Patients with R/R HGGExperimental treatment 1 intervention

Trial outcomes

Primary outcomes

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.

Time frame

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

Time frame