EGFR Gene MutationPhase 1NCT06186401
Anti-EGFRvIII synNotch Receptor Induced Anti-EphA2/IL-13Ralpha2 CAR (E-SYNC) T Cells
A Phase 1 study testing E-SYNC T Cells, Cyclophosphamide (non-investigational) and Fludarabine (non-investigational) in people with EGFR Gene Mutation and Glioblastoma, run by Hideho Okada, MD, PhD at 1 site in United States.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- EGFR Gene Mutation, Glioblastoma, MGMT-Unmethylated Glioblastoma
- What is being tested?
- E-SYNC T Cells, Cyclophosphamide (non-investigational) and Fludarabine (non-investigational)
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 20 participants
- Where
- 1 siteUnited States
- Study dates
- 30 Apr 2024to 31 Dec 2027
- Phase
- Phase 1
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
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- 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. Tissue Screening: Defines eligibility for tissue screening and to determine H-score.
- Study Enrollment: Defines eligibility for study enrollment and E-SYNC T cell manufacturing/treatment.
- Age >=18 years.
- Pathological criteria: EGFRvIII+ GBM from most recent surgery, confirmed by a Clinical Laboratory Improvement Amendments (CLIA)-certified lab using a next-generation sequencing panel.
- Karnofsky Performance Scale (KPS) score >=70.
- received at least standard of care external beam radiotherapy (SOC EBRT) as initial therapy, with or without concurrent temozolomide (TMZ), and completed the last dose of TMZ ≥23 days prior to study enrollment). Note: patients may have initiated adjuvant TMZ +/- TTFields.
- Pathological criteria: EGFRvIII+ GBM from most recent surgery, as defined by an EGFRvIII H-score of ≥ 150 based on central review.
- Is surgically amenable, with expectation for ability to resect at least 500 mg of tumor tissue confirmed by participant's neurosurgeon.
- Participants with reproductive potential agree to use reliable and double barrier method of contraception during the study and for at least 6 months after the last study intervention, including refraining from donating sperm during this period.
- Females of childbearing potential must have a negative serum beta-human chorionic gonadotropin (HCG) pregnancy test prior to receiving study interventions.
- All participants must have adequate organ function.
- Adequate bone marrow function is defined as: i. Peripheral absolute neutrophil account ≥ 1000/mm3 and ii. Platelet count ≥ 100,000/mm3 (transfusion dependent, defined as not receiving platelet transfusions for at least 7 days prior to enrollment) and iii. Absolute lymphocyte count (ALC) ≥ 300/µL and/or CD3 count of ≥ 150/µL b. Adequate renal function is defined as: i. Creatinine clearance or radioisotope glomerular filtration rate ≥ 50 mL/min/1.73m2 c. Adequate liver function is defined as: i. Total Bilirubin ≤ 1.5 x upper limit of normal (ULN) except for Gilbert's syndrome and ii. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 3 x ULN d. Coagulation tests prothrombin time (PT) and partial thromboplastin time (PTT) have to be within normal limits, unless the participant has been therapeutically anti-coagulated for previous venous thrombosis. e. Adequate pulmonary function, defined as no evidence of dyspnea at rest and pulse oximetry > 92% while breathing room air.
- Adequate cardiac function, confirmed within the last 12 months, defined as: i. Left ventricular ejection fraction (LVEF) ≥ 40% by echocardiogram or multi-gated acquisition scanning (MUGA)
- Must be willing to provide voluntary informed consent for study intervention.
Who cannot join
- 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.
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- 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.
- 1. Participant is unwilling to undergo another surgery if felt clinically appropriate.
- Prior treatment with any EGFR-targeting therapy
- Participant who has been treated with any investigational agents, chemotherapy, or biological therapy targeting GBM <= 4 weeks prior to date of study registration. Exceptions to this include: no TMZ <= 23 days or nitrosourea <= 6 weeks prior to study enrollment. There is no washout prior to study enrollment for TTFields, but use of the device must be stopped at least 1 week prior to initiation of lymphodepleting (LD) chemotherapy.
- 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.
- 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 inhaled, intranasal, ocular, topical, or other non-oral or non-IV steroids are not necessarily 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.
- Female participants who are pregnant or breast-feeding.
- 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.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
University of California, San Francisco
San Francisco, California, 94143
Neuro-Oncology New Patient Coordinator, 877-827-3222, NeuroOncNewPatientCoord@ucsf.edu
cancertrials@ucsf.edu
About this study
Official title: Phase 1 Study of Autologous Anti-EGFRvIII synNotch Receptor Induced Anti-EphA2/IL-13R alpha2 CAR (E-SYNC) T Cells in Adult Participants With EGFRvIII+ Glioblastoma
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.
Read the detailed description
PRIMARY OBJECTIVES:
- To determine the safety of IV infused E-SYNC T cells for the treatment of EGFRvIII positive (EGFRvIII+) glioblastoma (GBM) (both cohorts).
SECONDARY OBJECTIVES:
- To evaluate the feasibility of production and administration of E-SYNC T cells for the treatment of GBM (both cohorts).
II. To determine the local priming of E-SYNC T cells by prospective evaluation of GBM tissue and peripheral blood (cohort 2 only).
EXPLORATORY OBJECTIVES:
- To determine antitumor responses and survival after infusion of E-SYNC T cells.
II. To evaluate development of immune responses against E-SYNC T cells favoring rejection.
III. To characterize the intratumoral immune landscape.
OUTLINE: This is a dose-escalation study utilizing E-SYNC T cells.
COHORT 1 (Dose Escalation): An estimated 6 to 15 participants with newly diagnosed EGFRvIII+ glioblastoma with O6-methylguanine-DNA methyl-transferase (MGMT) unmethylated status who have completed initial radiation therapy will be assigned to cohort 1. Participants undergo leukapheresis for the creation of E-SYNC T cells at least 2 weeks after completion of their non-investigational, standard of care radiation therapy.
COHORT 2 (Tissue Cohort): Five participants with EGFRvIII+ glioblastoma who have residual disease present and surgery is clinically appropriate will be assigned to cohort 2. Participants undergo leukapheresis for the creation of E-SYNC T cells more than 2 weeks after completion of their non-interventional, standard of care radiation therapy. Participants also undergo standard of care (SOC) surgical resection.
After completion of study treatment, participants are followed up on days 1, 3, 7, 10, 14, 21, and 28, then every 4 weeks in weeks 8-24, every 8 weeks in weeks 32-48, every 12 weeks in weeks 60-96, every 3 months in months 24-36, and then annually in years 3-15.
NOTE: The product formulation has been adjusted as of Protocol Version 2.1. Due to this formulation change, the first 3 participants enrolled at DL 1 prior to the adjustment will not be counted towards dose escalation analysis. These participants will continue for safety evaluation. Starting with the 4th participant, new enrollees will receive the updated formulation and continue to enroll at DL 1 to ensure consistency in dosing escalation decisions. The 4th participant will therefore serve as the 1st participant in updated DL1 cohort. Hence, enrollment will be paused after 4th participant is treated in updated DL1 formulation and monitoring and subsequent infusions will proceed per the staggered schedule
- Being tested
- E-SYNC T Cells, Cyclophosphamide (non-investigational), Fludarabine (non-investigational), Leukapheresis, Surgical resection
- Keywords
- Immunotherapy, CAR T Therapy
- Medical subject headings
- Glioblastoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
E-SYNC T CellsBiological
Also called Anti-EGFRvIII synNotch Receptor Induced Anti-EphA2/IL-13R alpha2 CAR T Cells, Autologous Anti-EGFRvIII synNotch Receptor Induced Anti-EphA2/IL-13R alpha2 CAR T Cells, Autologous Anti-EGFRvIII synNotch Receptor Induced Anti-EphA2/IL-13Ra2 CAR T Cells
Given IV
Cyclophosphamide (non-investigational)Drug
Also called Cytoxan, Cytoxan Lyophilized, Neosar
Given IV
Fludarabine (non-investigational)Drug
Also called Fludara, Oforta
Given IV
LeukapheresisProcedure or surgery
Also called Therapeutic Leukopheresis
Undergo leukapheresis
Surgical resectionProcedure or surgery
Also called Resection
Undergo surgical resection of tumor tissue
| Study group | Role | What they receive |
|---|---|---|
| Cohort 1: Starting Dose Level 1 (5 x 10^7 CAR+ cells) (DL1) | Experimental | Participants with newly diagnosed EGFRvIII+ GBM with unmethylated MGMT promotor status will undergo leukapheresis for manufacturing of E-SYNC T cells at least 2 weeks after completion of non-interventional, standard of care radiation therapy. Participants receive cyclophosphamide IV and fludarabine IV on days -5, -4, and -3 and then receive E-SYNC T cells IV on day 0. Participants will receive a single infusion of drug product (DP) (5 x 10^7 CAR+ T cells) and be monitored for safety, presence of and possible synNotch > CAR-T priming of the DP in the peripheral blood. |
| Cohort 1: Dose-escalation Level 2 (1.5 x 10^8 CAR+ cells) (DL2) | Experimental | If there are no dose-limiting toxicities in the starting dose cohort, participants with newly diagnosed EGFRvIII+ GBM with unmethylated MGMT promotor status will undergo leukapheresis for manufacturing of E-SYNC T cells at least 2 weeks after completion of tnon-interventional, standard of care radiation therapy. Participants receive cyclophosphamide IV and fludarabine IV on days -5, -4, and -3 and then receive E-SYNC T cells IV on day 0. Participants will receive a single infusion of drug product (DP) (1.5 x 10^8 CAR+ T cells) and be monitored for safety, presence of and possible synNotch > CAR-T priming of the DP in the peripheral blood. Receives: Biological: E-SYNC T Cells; Drug: Cyclophosphamide (non-investigational); Drug: Fludarabine (non-investigational); Procedure: Leukapheresis |
| Cohort 2: Tissue analysis cohort | Experimental | Participants with EGFRvIII+ glioblastoma and residual disease appropriate for surgery will have EGFRvIII H-score assessed by digital image analysis of Immunohistochemistry (IHC) slides from the initial surgical sample, reflecting staining extent and intensity. Participants with H-score ≥150 who underwent initial tumor resection, completed non-investigational standard-of-care radiation therapy, and meet eligibility criteria will undergo leukapheresis to manufacture E-SYNC T cells at the maximum tolerated or recommended dose based on Cohort 1 results. Participants will receive lymphodepleting conditioning followed by a single drug product (DP) infusion on Day 0. After platelet recovery, participants will be hospitalized for non-investigational surgical resection approximately 2 weeks after DP infusion. Participants will be monitored for safety, DP synNotch > CAR-T priming, and anti-tumor response of E-SYNC T cells. Receives: Biological: E-SYNC T Cells; Drug: Cyclophosphamide (non-investigational); Drug: Fludarabine (non-investigational); Procedure: Leukapheresis; Procedure: Surgical resection |
What is being measured
The primary outcome is the main question the study is designed to answer.
Proportion of participants reporting treatment-emergent adverse events
Treatment-emergent adverse events will be graded by National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 5.0
Measured: Up to 96 weeks
Secondary outcomes (2)
Percentage of participants who successfully receive E-SYNC T cells
The percentage of participants for whom a sufficient quantity of drug product (E-SYNC T cells) could be manufactured from peripheral blood mononuclear cells (PBMC) obtained at apheresis and administered will be reported.
Measured: Up to 96 weeks
The percentage of primed E-SYNC T (Cohort 2 only) cells in TIL versus PBMC will be evaluated
The percentage of primed E-SYNC T cells in tumor-infiltrating lymphocytes (TIL) versus Peripheral blood mononuclear cell (PBMC) will be evaluated using single-cell RNA sequencing as a pilot study and described in 5 participants.
Measured: Up to 96 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Jan 2024
- Study start30 Apr 2024
- Primary completion31 Dec 2027 (estimated)
- Study completion31 Dec 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for EGFR Gene MutationStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 20 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Hideho Okada, MD, PhD
- Sponsor type
- University, hospital or other
- Collaborators
- California Institute for Regenerative Medicine (CIRM), National Cancer Institute (NCI)
- Responsible party
- Sponsor-investigator, Hideho Okada, MD, PhD, University of California, San Francisco
- Investigators
- Jennifer Clarke, MD, MPH, Study chair, University of California, San Francisco
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06186401
- Sponsor's protocol ID
- 23704
- Other IDs
- 5U19CA264338-03
- Status last verified
- Aug 2026
- First submitted
- 15 Dec 2023
- Last updated
- 13 Aug 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 13 Aug 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase 1 Study of Autologous Anti-EGFRvIII synNotch Receptor Induced Anti-EphA2/IL-13R alpha2 CAR (E-SYNC) T Cells in Adult Participants With EGFRvIII+ Glioblastoma
- ClinicalTrials.gov ID
- NCT06186401
- Acronym / sponsor ID
- 23704
- Keywords
- Immunotherapy, CAR T Therapy
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 20 participants (estimated)
- Lead sponsor
- Hideho Okada, MD, PhDUniversity, hospital or other
- Collaborators
- California Institute for Regenerative Medicine (CIRM), National Cancer Institute (NCI)
- Study start
- 30 Apr 2024 (actual)
- Primary completion
- 31 Dec 2027 (estimated)
- Study completion
- 31 Dec 2027 (estimated)
- First posted
- 2 Jan 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
PRIMARY OBJECTIVES:
- To determine the safety of IV infused E-SYNC T cells for the treatment of EGFRvIII positive (EGFRvIII+) glioblastoma (GBM) (both cohorts).
SECONDARY OBJECTIVES:
- To evaluate the feasibility of production and administration of E-SYNC T cells for the treatment of GBM (both cohorts).
II. To determine the local priming of E-SYNC T cells by prospective evaluation of GBM tissue and peripheral blood (cohort 2 only).
EXPLORATORY OBJECTIVES:
- To determine antitumor responses and survival after infusion of E-SYNC T cells.
II. To evaluate development of immune responses against E-SYNC T cells favoring rejection.
III. To characterize the intratumoral immune landscape.
OUTLINE: This is a dose-escalation study utilizing E-SYNC T cells.
COHORT 1 (Dose Escalation): An estimated 6 to 15 participants with newly diagnosed EGFRvIII+ glioblastoma with O6-methylguanine-DNA methyl-transferase (MGMT) unmethylated status who have completed initial radiation therapy will be assigned to cohort 1. Participants undergo leukapheresis for the creation of E-SYNC T cells at least 2 weeks after completion of their non-investigational, standard of care radiation therapy.
COHORT 2 (Tissue Cohort): Five participants with EGFRvIII+ glioblastoma who have residual disease present and surgery is clinically appropriate will be assigned to cohort 2. Participants undergo leukapheresis for the creation of E-SYNC T cells more than 2 weeks after completion of their non-interventional, standard of care radiation therapy. Participants also undergo standard of care (SOC) surgical resection.
After completion of study treatment, participants are followed up on days 1, 3, 7, 10, 14, 21, and 28, then every 4 weeks in weeks 8-24, every 8 weeks in weeks 32-48, every 12 weeks in weeks 60-96, every 3 months in months 24-36, and then annually in years 3-15.
NOTE: The product formulation has been adjusted as of Protocol Version 2.1. Due to this formulation change, the first 3 participants enrolled at DL 1 prior to the adjustment will not be counted towards dose escalation analysis. These participants will continue for safety evaluation. Starting with the 4th participant, new enrollees will receive the updated formulation and continue to enroll at DL 1 to ensure consistency in dosing escalation decisions. The 4th participant will therefore serve as the 1st participant in updated DL1 cohort. Hence, enrollment will be paused after 4th participant is treated in updated DL1 formulation and monitoring and subsequent infusions will proceed per the staggered schedule
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Cohort 1: Starting Dose Level 1 (5 x 10^7 CAR+ cells) (DL1) | Experimental | –Participants with newly diagnosed EGFRvIII+ GBM with unmethylated MGMT promotor status will undergo leukapheresis for manufacturing of E-SYNC T cells at least 2 weeks after completion of non-interventional, standard of care radiation therapy. Participants receive cyclophosphamide IV and fludarabine IV on days -5, -4, and -3 and then receive E-SYNC T cells IV on day 0. Participants will receive a single infusion of drug product (DP) (5 x 10^7 CAR+ T cells) and be monitored for safety, presence of and possible synNotch > CAR-T priming of the DP in the peripheral blood. |
| Cohort 1: Dose-escalation Level 2 (1.5 x 10^8 CAR+ cells) (DL2) | Experimental | Biological: E-SYNC T Cells, Drug: Cyclophosphamide (non-investigational), Drug: Fludarabine (non-investigational), Procedure: LeukapheresisIf there are no dose-limiting toxicities in the starting dose cohort, participants with newly diagnosed EGFRvIII+ GBM with unmethylated MGMT promotor status will undergo leukapheresis for manufacturing of E-SYNC T cells at least 2 weeks after completion of tnon-interventional, standard of care radiation therapy. Participants receive cyclophosphamide IV and fludarabine IV on days -5, -4, and -3 and then receive E-SYNC T cells IV on day 0. Participants will receive a single infusion of drug product (DP) (1.5 x 10^8 CAR+ T cells) and be monitored for safety, presence of and possible synNotch > CAR-T priming of the DP in the peripheral blood. |
| Cohort 2: Tissue analysis cohort | Experimental | Biological: E-SYNC T Cells, Drug: Cyclophosphamide (non-investigational), Drug: Fludarabine (non-investigational), Procedure: Leukapheresis, Procedure: Surgical resectionParticipants with EGFRvIII+ glioblastoma and residual disease appropriate for surgery will have EGFRvIII H-score assessed by digital image analysis of Immunohistochemistry (IHC) slides from the initial surgical sample, reflecting staining extent and intensity. Participants with H-score ≥150 who underwent initial tumor resection, completed non-investigational standard-of-care radiation therapy, and meet eligibility criteria will undergo leukapheresis to manufacture E-SYNC T cells at the maximum tolerated or recommended dose based on Cohort 1 results. Participants will receive lymphodepleting conditioning followed by a single drug product (DP) infusion on Day 0. After platelet recovery, participants will be hospitalized for non-investigational surgical resection approximately 2 weeks after DP infusion. Participants will be monitored for safety, DP synNotch > CAR-T priming, and anti-tumor response of E-SYNC T cells. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (31 listed)
- NOTE: There are two sets of eligibility criteria for Cohort 2. Tissue Screening: Defines eligibility for tissue screening and to determine H-score.
- Study Enrollment: Defines eligibility for study enrollment and E-SYNC T cell manufacturing/treatment.
Key exclusion criteria (22 listed)
- 1. Participant is unwilling to undergo another surgery if felt clinically appropriate.
- Participants who are currently using inhaled, intranasal, ocular, topical, or other non-oral or non-IV steroids are not necessarily excluded from the study.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| E-SYNC T CellsAlso: Anti-EGFRvIII synNotch Receptor Induced Anti-EphA2/IL-13R alpha2 CAR T Cells, Autologous Anti-EGFRvIII synNotch Receptor Induced Anti-EphA2/IL-13R alpha2 CAR T Cells, Autologous Anti-EGFRvIII synNotch Receptor Induced Anti-EphA2/IL-13Ra2 CAR T CellsGiven IV | Biological | Cohort 1: Dose-escalation Level 2 (1.5 x 10^8 CAR+ cells) (DL2), Cohort 2: Tissue analysis cohort |
| Cyclophosphamide (non-investigational)Also: Cytoxan, Cytoxan Lyophilized, NeosarGiven IV | Drug | Cohort 1: Dose-escalation Level 2 (1.5 x 10^8 CAR+ cells) (DL2), Cohort 2: Tissue analysis cohort |
| Fludarabine (non-investigational)Also: Fludara, OfortaGiven IV | Drug | Cohort 1: Dose-escalation Level 2 (1.5 x 10^8 CAR+ cells) (DL2), Cohort 2: Tissue analysis cohort |
| LeukapheresisAlso: Therapeutic LeukopheresisUndergo leukapheresis | Procedure or surgery | Cohort 1: Dose-escalation Level 2 (1.5 x 10^8 CAR+ cells) (DL2), Cohort 2: Tissue analysis cohort |
| Surgical resectionAlso: ResectionUndergo surgical resection of tumor tissue | Procedure or surgery | Cohort 2: Tissue analysis cohort |
Primary outcome
Proportion of participants reporting treatment-emergent adverse events
Time frame: Up to 96 weeks
Treatment-emergent adverse events will be graded by National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 5.0
2 secondary outcomes
Percentage of participants who successfully receive E-SYNC T cells
Time frame: Up to 96 weeks
The percentage of primed E-SYNC T (Cohort 2 only) cells in TIL versus PBMC will be evaluated
Time frame: Up to 96 weeks
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Aug 2026.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Jennifer Clarke, MD, MPH study chair
University of California, San Francisco
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing E-SYNC T Cells, Cyclophosphamide (non-investigational) and Fludarabine (non-investigational) in people with EGFR Gene Mutation and Glioblastoma, run by Hideho Okada, MD, PhD at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 31 inclusion and 22 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 13 Aug 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Neuro-Oncology New Patient Coordinator (877-827-3222, NeuroOncNewPatientCoord@ucsf.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Proportion of participants reporting treatment-emergent adverse events (time frame: Up to 96 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Aug 2026.