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

NCT06018363 | Recruiting Phase 1

• 1 other identifier: QH10401-GC-01（0）
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 1

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.

Conditions

Brain Gliomas; High-Grade Gliomas; GBM

Keywords

B7-H3; CAR-γδT; allogeneic

Outcome Measures

Primary Outcomes (4)

• 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 Outcomes (5)

• 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

Study Arms (1)

Patients with R/R HGG

EXPERIMENTAL

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

Interventions

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.

Patients with R/R HGG

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• )Age 18-70 years old (both ends included), both male and female;
• )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;
• \) 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;
• \) KPS ≥ 60 points;
• )Expected survival \> 3 months;
• )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.
• )No obvious hereditary diseases;
• )Normal cardiac function with cardiac ejection index \>55%;
• )No bleeding and coagulation disorders;
• )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;
• \) Sign the informed consent form.

You may not qualify if:

• )Pregnant and lactating women;
• )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;
• )patients with combined second tumors;
• )patients with active hepatitis B or C virus, HIV infection, or other untreated active infection;
• )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;
• )Current systemic use of steroid cell (except for recent or current use of inhaled steroids) substances;
• \) have a chronic disease requiring immunologic or hormonal therapy;
• \) have an allergy to immunotherapy and related cells;
• \) 10)Patients with a history of organ transplantation or who are awaiting organ transplantation;
• )Participation in other clinical trials within the previous 30 days;
• )Those who are not suitable for clinical trials for other reasons in the opinion of the investigator.

Sponsors & Collaborators

• Dushu Lake Hospital Affiliated to Soochow University: lead

Study Sites (1)

Dushu Lake Hospital Affiliated to Soochow University

Suzhou, Jiangsu, 215125, China

RECRUITING

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 25, 2023
• First Posted: August 30, 2023
• Study Start: June 1, 2023
• Primary Completion (Estimated): December 31, 2027
• Study Completion (Estimated): December 31, 2027
• Last Updated: August 19, 2025

Record last verified: 2025-08

Locations

CN (1)