Safety and Efficacy Study of TX103 CAR-T Cell Therapy for Recurrent or Progressive Grade 4 Glioma.

NCT06482905 | Recruiting Phase 1 FDA Drug

• 1 other identifier: TX103T-RG008
• Study Type: interventional
• Target: 52
• Locations: 2 countries
• Sites: 4

Brief Summary

This is a phase I, open-Label, single/multiple dose, dose-escalation study to evaluate the safety, tolerability and antitumor activity of anti-B7-H3 CAR-T cell injection (TX103) in subjects with recurrent or progressive Grade 4 Glioma.The study also plan to explore the Maximum Tolerated Dose (MTD) and determine the Recommended Phase II Dose (RP2D) of the CAR-T cell therapy.

Conditions

High-grade Glioma; WHO Grade Ⅳ Glioma

Outcome Measures

Primary Outcomes (2)

• Safety：Incidence of Dose Limiting Toxicity (DLT)

  Type, incidence, and severity of dose limiting toxicities (DLTs) within 28 days after the first TX103 infusion.

  28 days after the first TX103 infusion.

• Safety：Incidence and severity of adverse events (AEs)

  To evaluate the possible adverse events after TX103 infusion, including the incidence, and severity of AEs.

  six months post CAR-T cells infusion.

Secondary Outcomes (10)

• Overall survival (OS)

  6 and 12 months post CAR-T cells infusion.

• Post-relapse survival (PRS)

  6 and 12 months post CAR-T cells infusion.

• Progression Free Survival (PFS)

  1 year post CAR-T cells infusion.

• Disease Control Rate (DCR)

  1 year post CAR-T cells infusion.

• Duration of disease control (DDC)

  1 year post CAR-T cells infusion.

Other Outcomes (6)

• The immunogenicity of TX103

  up to 12 months.

• The positive rate of replication competent lentivirus tests

  up to 15 years.

• Incidence of Secondary Malignancies

  up to 15 years.

Study Arms (3)

Safety Run-In

EXPERIMENTAL

Single-dose administration of TX103 via intraventricular(ICV) or intracavitary (ICT) .

Biological: Anti-B7-H3 Chimeric Antigen Receptor T-Cell (CAR-T Cell) Injection/TX103

Cohort A Single delivery route(Multi-dose)

EXPERIMENTAL

Administration of TX103 via intraventricular(ICV) on Days 1 and 8 in a 21-day treatment cycle.

Biological: Anti-B7-H3 Chimeric Antigen Receptor T-Cell (CAR-T Cell) Injection/TX103

Cohort B Dual delivery route(Multi-dose)

EXPERIMENTAL

Administration of TX103 on Day 1 via intracavitary (ICT) and on Day 8 via intraventricular(ICV) in a 21-day treatment cycle.

Biological: Anti-B7-H3 Chimeric Antigen Receptor T-Cell (CAR-T Cell) Injection/TX103

Interventions

Anti-B7-H3 Chimeric Antigen Receptor T-Cell (CAR-T Cell) Injection/TX103 BIOLOGICAL

Safety Run-In: Dose:6×10\^7 CAR+ T cells Cohort A Single delivery route(Multi-dose)、Cohort B Dual delivery route(Multi-dose)： 3+3 dose escalation design： Dose Level 1: 6×10\^7 CAR+ T cells Dose Level 2: 1.5×10\^8 CAR+ T cells Dose Level 3: 2.5×10\^8 CAR+ T cells

Cohort A Single delivery route(Multi-dose); Cohort B Dual delivery route(Multi-dose); Safety Run-In

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subjects must voluntarily participate in the study and sign a written informed consent document; subjects should be willing and able to follow and complete study procedures.
• Male or female subjects aged 18 to 75 years (both inclusive).
• Subject must have histologically diagnosed grade 4 glioma, such as glioblastoma, grade 4 astrocytoma, diffuse hemispheric glioma, according to 2021 WHO Classification of Tumors of the CNS. Subjects must have had experienced disease recurrence or progression\* after surgery combined with Stupp regimen (concurrent radiotherapy and temozolomide (TMZ) followed by adjuvant TMZ) and are not candidate for re-resection. For subjects harboring specific gene mutations, such as NTRK gene fusion or BRAF V600E mutation, they must have also progressed on corresponding mutation-directed therapies before enrollment.
• \* Disease recurrence or progression must be confirmed by radiographic or histopathological diagnosis.
• Subjects with confirmed B7-H3 positive\* (≥30%) tumor expression by immunohistochemistry (IHC) in either primary or recurrent tumor tissue.
• \*B7-H3 positive rate is defined as the percentage of B7-H3 positive tumor cells in non-necrotic tumor tissue.
• Subjects with KPS score of ≥60.
• Subjects should have adequate venous access for collection of peripheral blood mononuclear cells (PBMCs).
• Subjects with left ventricular ejection fraction (LVEF) ≥ 40% within one month prior to the first dose.
• Subjects with oxygen saturation ≥95% under the resting state.
• Subjects with adequate organ function, as indicated by laboratory test results that meet the following criteria:
• Hematological function: Absolute neutrophil count (ANC) ≥1.5×109/L, hemoglobin (Hb) ≥90g/L, platelet count (PLT) ≥100×109/L, absolute lymphocytes count (ALC) ≥0.15×109/L. Blood transfusion, granulocyte (macrophage) colony stimulating factor, recombinant human erythropoietin, recombinant human thrombopoietin, platelet receptor agonist, recombinant human interleukin-11, and other supportive treatments are prohibited within 14 days before the test.
• Liver function: Total bilirubin (TBIL) ≤ 1.5 × ULN, patients with Gilbert's syndrome (persistent or recurrent hyperbilirubinemia, presenting as unconjugated bilirubin in the absence of evidence of hemolysis or liver pathology) Except for elevated erythrocytes; alanine aminotransferases (ALT) and aspartate aminotransferase (AST) ≤2.5×ULN.
• Renal function: serum creatinine (Scr) ≤1.5×ULN.
• Coagulation function (in the absence of anticoagulant therapy): prothrombin time (PT) or activated partial thromboplastin time (APTT) or international normalized ratio (INR) ≤ 1.5×ULN.

You may not qualify if:

• Pregnant or breastfeeding female subjects.
• Subjects with viral infection during the screening period:
• Serum HIV antibody positive, treponema pallidum serology positive; OR
• Hepatitis B surface antigen (HBsAg) positive and peripheral blood HBV DNA test value exceeds the normal range; OR
• Hepatitis C virus (HCV) antibody positive and peripheral blood HCV RNA positive.
• Medical history and concomitant diseases:
• Subjects who have received carmustine extended-release implantation surgery within 6 months;
• Subjects with known or suspected active autoimmune diseases, including but not limited to Crohn's disease, rheumatoid arthritis, systemic lupus erythematosus, etc.;
• Subjects who are receiving systemic immunosuppressive agents or subjects who need to use immunosuppressive agents for a long-time during treatment, except for intermittent topical, inhaled, or intranasal glucocorticoid therapy;
• Subjects with uncontrolled mental disorders, or who, in the Investigator's opinion, have a medical history or a history of mental states that may increase the risks associated with study participation or study drug administration, or that may interfere with the results;
• The toxicity and side effects caused by previous treatment have not recovered to ≤ grade 1 (per CTCAE 5.0); except for alopecia and other tolerable events judged by the Investigator;
• Subjects who have participated in other interventional clinical studies within the past 1 month;
• Subjects who have previously received CAR-T cell therapy or other gene therapy\*;
• Subjects with any serious or poorly controlled disease that, in the opinion of the Investigator, may increase the risk associated with study participation, study drug administration, or affect the subject's ability to receive study drug, including but not limited to cardiovascular and cerebrovascular diseases, renal insufficiency, pulmonary embolism, coagulopathy or requiring long-term anticoagulant therapy, active infection or uncontrollable infection requiring long-term systemic treatment;
• Subjects with other malignant tumors in the past 3 years or at present, except for non-melanoma skin cancer, carcinoma in situ (such as cervix, bladder and breast cancer).

Sponsors & Collaborators

• Tcelltech Inc.: lead
• Beijing Tiantan Hospital: collaborator
• Mayo Clinic: collaborator

Study Sites (4)

Mayo Clinic in Arizona

Phoenix, Arizona, 85054, United States

RECRUITING

Mayo Clinic in Florida

Jacksonville, Florida, 32224, United States

RECRUITING

Mayo Clinic in Rochester

Rochester, Minnesota, 55905, United States

RECRUITING

Beijing Tiantan Hospital

Beijing, Beijing Municipality, 100730, China

RECRUITING

MeSH Terms

Conditions

Glioma

Interventions

Immunotherapy, Adoptive; Injections

Condition Hierarchy (Ancestors)

Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Intervention Hierarchy (Ancestors)

Adoptive Transfer; Immunization, Passive; Immunization; Immunotherapy; Immunomodulation; Biological Therapy; Therapeutics; Immunologic Techniques; Investigative Techniques; Drug Administration Routes; Drug Therapy

Study Officials

• Gangxiong Huang, MD

  Tcelltech Inc.

  STUDY DIRECTOR

Central Study Contacts

Rui Feng, MD

CONTACT

+(86)13509312934; fengrui@tcelltech.com

Xianzhen Chen, MM

CONTACT

+(86)18649725652; chenxianzhen@tcelltech.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: a "3+3" design is used to determine Maximum Tolerated Dose (MTD) and the recommended phase 2 dose (RP2D)

Study Record Dates

• First Submitted: June 15, 2024
• First Posted: July 1, 2024
• Study Start: September 4, 2024
• Primary Completion (Estimated): September 1, 2026
• Study Completion (Estimated): June 1, 2027
• Last Updated: March 24, 2026

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (3); CN (1)