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

Официальное название

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

Обзор

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.

Вмешательства

• Биопрепарат 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.

Первичные конечные точки

• Phase 1: Incidence of Adverse Events (AEs) [Срок оценки: 12 months]
• Phase 1:Incidence of Dose-Limiting Toxicities (DLTs) [Срок оценки: 28 days after the first dose of B7-H3 CAR-γδT cells]
• Phase 1:Maximum tolerated dose (MTD) [Срок оценки: 28 days after the first dose of B7-H3 CAR-γδT cells]
• Phase 1: Recommended phase 2 dose (RP2D) [Срок оценки: 28 days after the first dose of B7-H3 CAR-γδT cells]

Вторичные конечные точки (5)

• Pharmacokinetics: copy number of B7-H3 CAR-γδT cells in cerebrospinal fluid(CSF) [Срок оценки: 28 days after the first dose of B7-H3 CAR-γδT cells]
• Pharmacodynamics: Peak level of cytokines in CSF [Срок оценки: 28 days after the first dose of B7-H3 CAR-γδT cells]
• Phase 2: Overall survival (OS) [Срок оценки: 6 months, 9 months and 12 months]
• Phase 2: Progression Free Survival (PFS) [Срок оценки: 6 months]
• Disease Control Rate (DCR) [Срок оценки: 6 months]

Критерии участия

Критерии включения

• 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.

Критерии исключения

• 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.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Не применимо

Модель

Последовательный дизайн

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Китай · 1 центр

• Dushu Lake Hospital Affiliated to Soochow University — Сучжоу

Идентификаторы

NCT: NCT06018363 · QH10401-GC-01（0）

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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