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

Official title

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

Overview

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.

Interventions

• 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.

Primary outcome measures

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

Secondary outcome measures (5)

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

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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Sequential

Masking

Open label

Primary purpose

Treatment

Study locations

China · 1 center

• Dushu Lake Hospital Affiliated to Soochow University — Suzhou

Identifiers

NCT: NCT06018363 · QH10401-GC-01（0）

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗