Anti-EGFRvIII synNotch Receptor Induced Anti-EphA2/IL-13Ralpha2 CAR (E-SYNC) T Cells

Recruiting now · Phase 1

Conditions studied: EGFR Gene Mutation, Glioblastoma, MGMT-Unmethylated Glioblastoma, Recurrent Glioblastoma

In brief

This phase I trial tests the safety, side effects, and best dose of E-SYNC chimeric antigen receptor (CAR) T cells after lymphodepleting chemotherapy in treating patients with EGFRvIII positive (+) glioblastoma. Chimeric antigen receptor (CAR) T-cell therapy is a type of treatment in which a patient's T cells (a type of immune system cell) are changed in the laboratory so the CAR T cells will attack cancer cells. T cells are taken from a patient's blood. Then the gene for a special receptor that binds to a certain protein on the patient's cancer cells is added to the T cells in the laboratory. The special receptor is called a chimeric antigen receptor. Large numbers of the CAR T cells are grown in the laboratory and given to the patient by infusion for treatment of certain cancers. Lymphodepleting chemotherapy with cyclophosphamide and fludarabine before treatment with CAR T cells may make the CAR T cells more effective.

Key facts

Study ID

NCT06186401

Run by

Hideho Okada, MD, PhD

People needed

20

Starts

2024-04-30

Expected to finish

2027-12-31

Last updated by the study team

2026-03-16

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• Inclusion Criteria for Cohort 1:
• Age >= 18 years.
• Karnofsky performance status (KPS) score of >=70.
• All participants must have adequate organ function defined as:
• Peripheral absolute neutrophil count >=1000/mm\^3.
• Platelet count >=100,000/mm\^3 (transfusion independent, defined as not receiving platelet transfusions for at least 7 days prior to enrollment).
• Absolute lymphocyte count (ALC) >= 300/μL and/or Cluster of differentiation 3 (CD3) count of >=150/μL.
• Creatinine clearance or radioisotope glomerular filtration rate >= 50 mL/min/1.73m\^2.
• Total Bilirubin <= 1.5 x ULN except for Gilbert's syndrome and
• Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) <= 3x upper limit of normal (ULN).
• Left ventricular ejection fraction (LVEF) >= 50% by echocardiogram or multi-gated acquisition scanning (MUGA).
• Adequate pulmonary function, defined as no evidence of dyspnea at rest and pulse oximetry > 92% while breathing room air.
• Pathological criteria: EGFRvIII+ GBM from most recent surgery, confirmed by a Clinical Laboratory Improvement Amendments (CLIA)-certified lab using a next-generation sequencing panel.
• MGMT promoter must be unmethylated or with a methylation index < 3.
• Must have completed at least standard of care (SOC) external beam radiotherapy (EBRT) as initial therapy.
• Participants must be anticipated to be able to complete E-SYNC T cell infusion within 12 weeks after completion of EBRT.
• All participants must be off systemic steroids for 3 days or more prior to leukapheresis.
• Must be willing to provide voluntary informed consent for apheresis (and tissue screening if needed) and for study treatment.
• NOTE: There are two sets of eligibility criteria for Cohort 2. Step 1 defines eligibility for tissue screening and apheresis, and Step 2 defines eligibility for study enrollment and E-SYNC T cell treatment.
• Inclusion Criteria for Cohort 2, Step 1:
• Age >=18 years.
• KPS score >=70.
• All participants must have adequate organ function defined as:
• Peripheral absolute neutrophil count >=1000/mm\^3.
• Platelet count >=100,000/mm\^3 (transfusion independent, defined as not receiving platelet transfusions for at least 7 days prior to enrollment).

You may not qualify if…

• Exclusion Criteria for Cohort 1
• Participant who has been treated with any investigational agents and chemotherapy targeting GBM <= 4 weeks prior to date of study registration. Exceptions to this include: must be >=23 days from last dose of temozolomide (TMZ) or radiotherapy, mush be >= 6 weeks from last dose of nitrosourea.
• Female participants of reproductive potential who are pregnant or lactating. Female study participants of reproductive potential must have a negative serum pregnancy test as part of eligibility confirmation.
• Known addiction to alcohol or illicit drugs.
• Prior treatment with any Epithelial Growth Factor Receptor (EGFR)-targeting therapy.
• Participants with leptomeningeal dissemination.
• Participants with a known disorder that affects their immune system, such as human immunodeficiency virus (HIV) or an autoimmune disorder requiring systemic cytotoxic or immunosuppressive therapy. Participants who are currently using non-systemic steroids (e.g., inhaled, intranasal, ocular, topical) are not excluded from the study.
• Participants with serologic status reflecting active hepatitis B or C infection. Participants that are positive for hepatitis B surface antigen (HBsAg+) will be excluded. Participants that are positive for hepatitis B core antibody or hepatitis C antibody must have a negative polymerase chain reaction (PCR) prior to enrollment. PCR positive participants will be excluded.
• Participants who have received prior solid organ or bone marrow transplantation.
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, second cancer currently receiving active treatment or anticipated to receive treatment within the next year, or psychiatric illness/social situations that would limit compliance with study requirements.
• Participants who are unable to return for follow-up visits or obtain follow-up studies required to assess toxicity to therapy.
• Exclusion Criteria for Step 1 for Cohort 2
• Participant who has been treated with any investigational agents or chemotherapy targeting GBM <=4 weeks prior to date of study registration. Exceptions to this include: must be>= 23 days from last dose of TMZ or radiotherapy, must be>=6 weeks from last dose of nitrosourea.
• Female participants of reproductive potential who are pregnant or lactating. Female study participants of reproductive potential must have a negative serum pregnancy test as part of Step 1 eligibility confirmation.
• Uncontrolled active infection.
• Participants with a known disorder that affects their immune system, such as HIV or an autoimmune disorder requiring systemic cytotoxic or immunosuppressive therapy.
• Participants who are currently using non-systemic steroids (e.g., inhaled, intranasal, ocular, topical) are not excluded from the study.
• Participants with serologic status reflecting active hepatitis B or C infection. Participants that are positive for hepatitis B surface antigen (HBsAg+) will be excluded. Participants that are positive for hepatitis B core antibody or hepatitis C antibody must have a negative polymerase chain reaction (PCR) prior to enrollment. PCR positive participants will be excluded.
• Known addiction to alcohol or illicit drugs.
• Exclusion Criteria for Step 2 for Cohort 2
• Prior to Step 2, participants must have undergone leukapheresis in Step 1. In addition:
• Prior treatment with any EGFR-targeting therapy
• Participant who has been treated with any investigational agents or chemotherapy targeting GBM <= 4 weeks prior to date of study registration. Exceptions to this include: must be >= 23 days from last dose of TMZ or radiotherapy, must be >= 6 weeks from last dose of nitrosourea.
• Participants with imaging or clinical evidence of uncontrolled tumor mass effect; the assessment of mass effect will be made by the Investigators.
• Participants with leptomeningeal dissemination.

Where it is running

• University of California, San Francisco — San Francisco, California, United States (enrolling)

Full record on ClinicalTrials.gov

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