QH104 (allogeneic B7-H3 CAR γδT) for malignant brain glioma

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

This study will test if injections of allogeneic B7‑H3 CAR γδT cells (QH104) can help adults with B7‑H3–positive recurrent or progressive high‑grade glioma, including GBM.

Quick facts

• Phase: Phase1; Phase2
• Study type: Interventional
• Enrollment: 25 (estimated)
• Ages: 18 Years to 70 Years
• Sex: All
• Sponsor: Dushu Lake Hospital Affiliated to Soochow University (Academic / other)
• Drugs / interventions: immunotherapy
• Locations: 1 site (Suzhou, Jiangsu)
• Trial ID: NCT06018363 on ClinicalTrials.gov

What this trial studies

B7‑H3 is highly expressed on many high‑grade glioma cells and tumor-associated endothelial cells, making it an attractive immunotherapy target. QH104 uses allogeneic γδ T cells engineered with a CAR targeting B7‑H3; γδ T cells can recognize tumor cells without MHC restriction and have lower risk of graft‑versus‑host disease. The study is an open‑label, single‑arm dose‑escalation followed by dose‑expansion trial to characterize safety and early signs of anti‑tumor activity. Eligible adults must have B7‑H3–positive, histologically confirmed WHO grade 3–4 glioma with measurable disease and adequate performance status and organ function, and all treatment and follow‑up occur at the sponsoring site in Suzhou, China.

Who should consider this trial

Good fit: Adults 18–70 with histologically confirmed WHO grade 3–4 glioma (including GBM) that has progressed after prior therapy, with B7‑H3–positive tumor tissue, KPS ≥60, expected survival >3 months, and adequate marrow, liver, and renal function are ideal candidates.

Not a fit: Patients with B7‑H3–negative tumors, poor performance status, life expectancy under three months, or significant organ dysfunction are unlikely to benefit from this therapy.

Why it matters

Potential benefit: If successful, QH104 could shrink tumors or slow progression and provide an off‑the‑shelf immunotherapy option for patients with B7‑H3–positive high‑grade gliomas with a lower risk of graft‑versus‑host disease than conventional allogeneic T cells.

How similar studies have performed: Early‑phase trials of B7‑H3–targeted CAR therapies and of allogeneic γδ T cell approaches have shown preliminary anti‑tumor signals but clinical effectiveness remains limited and not yet proven.

Eligibility criteria

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.

Where this trial is running

Suzhou, Jiangsu

• Dushu Lake Hospital Affiliated to Soochow University — Suzhou, Jiangsu, China (Recruiting)

Conditions Brain Gliomas; High-Grade Gliomas; GBM; B7-H3; CAR-γδT; allogeneic