Safety and Preliminary Efficacy of a Metabolically Armed Chimeric Antigen Receptor T Cell Therapy Targeting EGFRvIII for Recurrent Glioblastoma

NCT07244666 | Not Yet Recruiting Early Phase 1

• 1 other identifier: META10-EGFRvⅢ-010
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 1

Brief Summary

A Study of Metabolically Armed EGFRvII CAR-T Cells Therapy for Patients With Recurrent Glioblastoma

Conditions

Glioblastoma (GBM)

Keywords

Recurrent glioblastoma; EGFRvIII; metabolically armed; IL-10; CAR-T Cells Therapy

Outcome Measures

Primary Outcomes (1)

• Adverse Events (AEs)

  To characterize the safety profile of Meta10-EGFRvIII in patients with recurrent glioblastoma as assessed by incidence of adverse events. Adverse events will be graded by the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 5.0.

  up to 12 months

Secondary Outcomes (1)

• Objective response rate (ORR)

  1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12 months after receiving the first dose of CAR-T cell infusion

Study Arms (1)

Administration of Metabolically Armed EGFRvIII CAR-T cells

EXPERIMENTAL

Patients will be assigned to either the intraventricular injection group or the intravenous injection group, and receive a single infusion of Meta10-EGFRvIII on Day 0.

Drug: Metabolically Armed EGFRvIII CAR-T cells

Interventions

Metabolically Armed EGFRvIII CAR-T cells DRUG

Patients will receive a single infusion of Meta10-EGFRvIII.

Also known as: Meta10-EGFRvIII, LMC005

Administration of Metabolically Armed EGFRvIII CAR-T cells

Eligibility Criteria

• Age: 19 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• All subjects or their legal guardians must personally sign the written informed consent form approved by the ethics committee in writing before starting any screening procedures;
• Age between 18 and 70 years old (inclusive), both male and female;
• Confirmed diagnosis of recurrent glioblastoma, as specified below:
• Previously diagnosed with glioblastoma through histopathological/ molecular pathology reports.
• Disease progression or recurrence confirmed by histopathology or imaging (defined as per RANO2.0 criteria as either progression/recurrence or lesions with abnormal enhancement accompanied by hypermetabolism or hyperperfusion changes) that are eligible for use when no standard treatment is available at enrollment;
• Positive EGFRvIII expression detected in tumor cells (confirmed through next-generation sequencing), and only eligible for patients who have previously received EGFRvIII-targeted therapy and relapsed, provided the EGFRvIII remains positive in post-relapse tumor samples;
• Karnofsky Performance Status (KPS) ≥60 points, ECOG score ≤2 (reconfirmed before CAR-T infusion);
• Measurable tumor lesions according to the Response Assessment in Neuro-Oncology (RANO 2.0);
• Adequate peripheral blood obtainable via venipuncture with no contraindications for lymphocyte collection, and sufficient peripheral blood cells collected for CAR-T cell preparation;
• Expected life expectancy ≥12 weeks;
• Adequate organ function (reconfirmed before CAR-T infusion):
• Complete blood count \[must meet the following criteria within 24 hours prior to whole blood collection: avoid transfusions, platelet transfusions, and colony-stimulating factors (excluding recombinant erythropoietin) within 7 days before testing\]:
• Blood Biochemistry: Serum alanine aminotransferase (ALT)/aspartate aminotransferase (AST) ≤2.5 times ULN; serum creatinine ≤1.6 mg/dL; total bilirubin ≤1.5 mg/dL (except for subjects with GBM liver involvement and Gilbert syndrome patients, whose total bilirubin must be \<3.0 mg/dL).
• Serology: Human immunodeficiency virus (HIV) antibody seronegative. The hepatitis B antigen test is negative, and the hepatitis C antibody test is negative. If the hepatitis C antibody test is positive, reverse transcription polymerase chain reaction (RT-PCR) must be performed to detect the presence of hepatitis B antigen and confirm that the hepatitis C virus (HCV) RNA is negative.
• Lung function: normal or grade 1 dyspnea according to CTCAE, SaO2 ≥ 92% in indoor air environment.

You may not qualify if:

• Subjects exhibiting other severe central nervous system disorders deemed by the investigator to be unrelated to the indication;
• Subjects anticipated to require systemic corticosteroid use within three months due to disease progression related to the indication;
• Subjects who have received the following medications:
• Corticosteroids at therapeutic doses (defined as prednisone \>20 mg/day, hydrocortisone \>20 mg/day, methylprednisolone \>4 mg/day, dexamethasone \>0.75 mg/day, betamethasone \>0.5 mg/day) within 7 days prior to leukapheresis or within 72 hours before CAR-T cell administration;
• Lymphocyte-toxic chemotherapy (e.g., cyclophosphamide, ifosfamide, bendamustine) administered within 2 weeks prior to leukapheresis;
• Investigational drugs from other clinical trials used within 4 weeks prior to blood collection. Exception: Patients whose prior trial medications were ineffective or whose disease progressed during the trial, provided at least 3 half-lives have elapsed since the last dose before leukapheresis;
• Radiotherapy received within 4 weeks prior to blood collection.
• Subjects with active hepatitis B (defined as hepatitis B surface antigen positivity or core antibody positivity with HBV DNA \>1000 copies/mL) or active hepatitis C (HCV RNA positive);
• Subjects testing positive for HIV antibodies or Treponema pallidum antibodies;
• Subjects with uncontrolled acute life-threatening bacterial, viral, or fungal infections (e.g., positive blood culture ≤72 hours prior to LMC005 infusion);
• Subjects with unstable angina and/or myocardial infarction within 6 months prior to signing informed consent; or subjects with severe stroke or deep venous thrombosis (DVT) within 12 months prior to signing informed consent;
• Subjects with a history of or concurrent malignant tumors, except those meeting the following criteria:
• Surgically excised non-melanoma skin cancer;
• Curatively treated carcinoma in situ of the cervix;
• Localized prostate cancer;

Sponsors & Collaborators

• Second Affiliated Hospital, School of Medicine, Zhejiang University: lead
• Leman Biotech Co., Ltd.: collaborator

Study Sites (1)

The Second Affiliated Hospital Zhejiang University School of Medicine

Hangzhou, Zhejiang, China

Location

MeSH Terms

Conditions

Glioblastoma

Condition Hierarchy (Ancestors)

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

Study Officials

• Chongran Sun, PhD

  Second Affiliated Hospital, School of Medicine, Zhejiang University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Chongran Sun, PhD

CONTACT

86+15925612402; 2307010@zju.edu.cn

Study Design

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

Study Record Dates

• First Submitted: November 17, 2025
• First Posted: November 24, 2025
• Study Start: November 15, 2025
• Primary Completion (Estimated): December 31, 2027
• Study Completion (Estimated): December 31, 2028
• Last Updated: November 24, 2025

Record last verified: 2025-10

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)