Recruiting PHASE1 EGFR Gene Mutation

New treatment option for EGFR Gene Mutation

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

ClinicalTrials.gov ID: NCT06186401

What this study is testing

What is E-SYNC T Cells?

E-SYNC T Cells is an investigational medicine, given as an infusion into a vein, being studied as a potential treatment for egfr gene mutation.

Also referred to as 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.

Plain-language explanation of the investigational treatment - it is being studied and is not an approved or proven therapy. The study team can confirm the details.

What it's testing: 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.

Phase 1: an early, usually small safety study

A plain-language read of the study's public ClinicalTrials.gov listing. The study team confirms the details.

Who can take part

Ages 18 and older

You may be able to join if

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.

You likely can't join if

Exclusion Criteria for Cohort 1
Participant who has been treated with any investigational agents and chemotherapy targeting GBM \ =23 days from last dose of temozolomide (TMZ) or...
Female participants of reproductive potential who are pregnant or lactating. Female study participants of reproductive potential must have a negative...
Known addiction to alcohol or illicit drugs.
Prior treatment with any Epithelial Growth Factor Receptor (EGFR)-targeting therapy.
Participants with leptomeningeal dissemination.

See the full eligibility criteria

Who can join

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...
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).
Absolute lymphocyte count (ALC) \>= 300/μL and/or 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, as defined by an EGFRvIII + H-score of \>=250 based on central review.
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).
for Cohort 2, Step 2. Note: Prior to Step 2, participants must have undergone leukapheresis in Step 1. In addition:
KPS score \>=70.
Must have received at least SOC EBRT as initial therapy; any number of prior recurrences is allowed.
Pathological criteria: EGFRvIII+ GBM from most recent surgery, as defined by an EGFRvIII + H-score of \>=250 based on central review.
Must have radiographic progression consistent with the Response assessment in neuro-oncology criteria (RANO) criteria for progressive disease (PD)
Recurrence must be surgically amenable, with expectation for ability to resect at least 500mg of tumor tissue
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...
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 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 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).
Coagulation tests prothrombin time (PT) and partial thromboplastin time (PTT) have to be within normal limits, unless the participant has been therapeutically anticoagulated for previous venous thrombosis.
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 left ventricular ejection fraction (LVEF) \>= 40% by echocardiogram or multi-gated acquisition scanning (MUGA).
Must be willing to provide voluntary informed consent for apheresis (and tissue screening if needed).

What rules you out

Exclusion Criteria for Cohort 1
Participant who has been treated with any investigational agents and chemotherapy targeting GBM \ =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...
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...
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...
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 \ = 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...
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...
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 \ = 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.
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...
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...
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...
Participants who are unable to return for follow-up visits or obtain follow-up studies required to assess toxicity to therapy.

The study team makes the final eligibility decision.

Where it's taking place

San Francisco, California, United States

Questions & answers

Do participants get paid in this trial?

This listing doesn't specify compensation. Many trials still reimburse travel or offer a stipend, so it's worth asking the study team when you connect.

Is it free to join, and do I need insurance?

Searching and applying through BridgeMD is free. In clinical trials the study-related treatment and visits are generally provided at no cost to you. You usually don't need insurance to take part - confirm specifics with the study team.

How long does this study last?

The listing doesn't state an exact length. The study team walks you through the schedule and number of visits before you decide to enroll.

Who can join this trial?

This study is enrolling all sexes, 18 years and older. The study team makes the final eligibility decision.

Where is this trial taking place?

Study sites include San Francisco, California, United States. Enter your location above to see the nearest site and check your eligibility.

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BridgeMD is an information and trial-matching tool - not medical advice, and not the study sponsor. Details come from ClinicalTrials.gov; the study team decides eligibility.