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

Phase 1

Recruiting

• Conditions: Brain Gliomas; High-Grade Gliomas; GBM
• Interventions: Biological: Allogenic B7-H3 CAR-γδT cell(QH104)

• Registration Number: NCT06018363
• Lead Sponsor: Dushu Lake Hospital Affiliated to Soochow University

Brief Summary

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.

Detailed Description

γδT cells are known as "a great candidate for car-t cells". Although they only account for 2% - 5% of all T cells in our body, they are a natural killer.

Treatment on this study includes six B7H3 CAR-γδ Tcell infusions over an 12 week period. B7H3 CAR-γδ T cells will be locoregionally administered via a CNS reservoir catheter without lymphodepleting chemotherapy. The study will evaluate the safety, feasibility and maximum tolerated dose (MTD) of B7H3 CAR-γδ T cell using a 3+3 study design and an 4 week evaluation period. The total study duration will be 2 years.

Study Timeline

• Study Start: 2023-06-01
• Study First Submitted: 2023-08-25
• Study First Submitted QC: 2023-08-25
• Study First Posted: 2023-08-30
• Status Verified: 2025-08
• Last Update Submitted: 2025-08-13
• Last Update Posted: 2025-08-19
• Primary Completion: 2027-12-31
• Study Completion: 2027-12-31

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 25

Inclusion Criteria

• 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;
• 5)Expected survival > 3 months;
• 6)Substantially normal bone marrow reserve function and normal liver and renal function (laboratory tests need to be fulfilled before receiving QH104 Cell Injection for the first time):White blood cell count (WBC) ≥ 3 x 10^9/L;Lymphocyte count (LY) ≥ 0.8 x 10^9/L;Hemoglobin (Hb) ≥ 90g/L;Platelet (PLT) ≥80×10^9/L;Albumin transaminase (ALT) & albumin transaminase (AST) <1.5×ULN;Serum creatinine (Cr) <1.5 x ULN;Total bilirubin < 1.5 x ULN;PT & PTT ≤ 1.25 x ULN.
• 7)No obvious hereditary diseases;
• 8)Normal cardiac function with cardiac ejection index >55%;
• 9)No bleeding and coagulation disorders;
• 10)Women of childbearing age (15-49 years old) must have had a pregnancy test with a negative result within 7 days prior to the start of treatment, and subjects are willing to use contraception during the clinical trial and for 3 months after the last cell infusion;
• 11. Sign the informed consent form.

Exclusion Criteria

• 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;
• 5)any severe, uncontrolled systemic autoimmune disease or any unstable systemic disease, including but not limited to systemic lupus erythematosus, rheumatoid arthritis, ulcerative colitis, Crohn's disease, and temporal arteritis;
• 6)Current systemic use of steroid cell (except for recent or current use of inhaled steroids) substances;
• 7. have a chronic disease requiring immunologic or hormonal therapy;
• 8. have an allergy to immunotherapy and related cells;
• 9. 10)Patients with a history of organ transplantation or who are awaiting organ transplantation;
• 10)Participation in other clinical trials within the previous 30 days;
• 11)Those who are not suitable for clinical trials for other reasons in the opinion of the investigator.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Patients with R/R HGG	Allogenic B7-H3 CAR-γδT cell(QH104)	-

Primary Outcome Measures

Name	Time	Method
Phase 1: Incidence of Adverse Events (AEs)	12 months	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.
Phase 1:Incidence of Dose-Limiting Toxicities (DLTs)	28 days after the first dose of B7-H3 CAR-γδT cells	DLT was defined as B7-H3 CAR-γδT cells-related events with onset within first 28 days following infusion
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

Secondary Outcome Measures

Name	Time	Method
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
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

Trial Locations

Locations (1)

Dushu Lake Hospital Affiliated to Soochow University; 🇨🇳 Suzhou, Jiangsu, China