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

Allogeneic B7-H3 CAR-γδT Cell Therapy Recurrent/Progressive High Grade Glioma（R/R HGG）

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.

Study Overview

• Status: Recruiting
• Conditions: GBM; High-Grade Gliomas; Brain Gliomas
• Intervention / Treatment: Biological: Allogenic B7-H3 CAR-γδT cell(QH104)

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 Type: Interventional
• Enrollment (Estimated): 25
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• China
  • Jiangsu
    • Suzhou, Jiangsu, China, 215125
      • Recruiting
      • Dushu Lake Hospital Affiliated to Soochow University
      • Contact: Yulun Huang; Phone Number: +86 130 1388 9432; Email: huangyulun@suda.edu.cn
      • Contact: Xuetao Li; Phone Number: +86 151 9563 7789; Email: lixuetao0405@126.com
      • Principal Investigator: Yulun Huang
      • Sub-Investigator: Xuetao Li

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Patients with R/R HGG

Biological: Allogenic B7-H3 CAR-γδT cell(QH104); 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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

Secondary Outcome Measures

Outcome Measure	Time Frame
Disease Control Rate (DCR)	6 months
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

Collaborators and Investigators

• Sponsor: Dushu Lake Hospital Affiliated to Soochow University

Study record dates

Study Major Dates

• Study Start (Actual): June 1, 2023
• Primary Completion (Estimated): December 31, 2027
• Study Completion (Estimated): December 31, 2027

Study Registration Dates

• First Submitted: August 25, 2023
• First Submitted That Met QC Criteria: August 25, 2023
• First Posted (Actual): August 30, 2023

Study Record Updates

• Last Update Posted (Actual): August 19, 2025
• Last Update Submitted That Met QC Criteria: August 13, 2025
• Last Verified: August 1, 2025

More Information

Terms related to this study

• Keywords: allogeneic; B7-H3; CAR-γδT
• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Glioma
• Other Study ID Numbers: QH10401-GC-01（0）

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No