NCT06186401 Anti-EGFRvIII synNotch Receptor Induced Anti-EphA2/IL-13Ralpha2 CAR (E-SYNC) T Cells
| NCT ID | NCT06186401 |
| Status | Recruiting |
| Phase | Phase 1 |
| Sponsor | Hideho Okada, MD, PhD |
| Condition | EGFR Gene Mutation |
| Study Type | INTERVENTIONAL |
| Enrollment | 20 participants |
| Start Date | 2024-04-30 |
| Primary Completion | 2027-12-31 |
Eligibility & Interventions
Eligibility Fast-Check
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What to Expect as a Participant
You will actively receive the study intervention — which may be a drug, biologic, device, or procedure.
Phase 1 is the earliest stage of human testing — safety and dosage are the primary focus. Visits are frequent and medical supervision is intensive. You will be among the first people to receive this treatment.
This trial targets 20 participants in total. It began in 2024-04-30 with a primary completion date of 2027-12-31.
⚠ This information is for research awareness only. Always consult your physician before joining any clinical trial. Participation is voluntary and you may withdraw at any time.
Brief 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. 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.
Eligibility Criteria
Inclusion Criteria: * Inclusion Criteria for Cohort 1: 1. Age \>= 18 years. 2. Karnofsky performance status (KPS) score of \>=70. 3. All participants must have adequate organ function defined as: 1. Peripheral absolute neutrophil count \>=1000/mm\^3. 2. Platelet count \>=100,000/mm\^3 (transfusion independent, defined as not receiving platelet transfusions for at least 7 days prior to enrollment). 3. Absolute lymphocyte count (ALC) \>= 300/μL and/or Cluster of differentiation 3 (CD3) count of \>=150/μL. 4. Creatinine clearance or radioisotope glomerular filtration rate \>= 50 mL/min/1.73m\^2. 5. Total Bilirubin \<= 1.5 x ULN except for Gilbert's syndrome and 6. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) \<= 3x upper limit of normal (ULN). 7. Left ventricular ejection fraction (LVEF) \>= 50% by echocardiogram or multi-gated acquisition scanning (MUGA). 8. Adequate pulmonary function, defined as no evidence of dyspnea at rest and pulse oximetry \> 92% while breathing room air. 4. Pathological criteria: EGFRvIII+ GBM from most recent surgery, confirmed by a Clinical Laboratory Improvement Amendments (CLIA)-certified lab using a next-generation sequencing panel. 5. MGMT promoter must be unmethylated or with a methylation index \< 3. 6. Must have completed at least standard of care (SOC) external beam radiotherapy (EBRT) as initial therapy. 7. Participants must be anticipated to be able to complete E-SYNC T cell infusion within 12 weeks after completion of EBRT. 8. All participants must be off systemic steroids for 3 days or more prior to leukapheresis. 9. 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. * Inclusion Criteria for Tissue Screening Cohort 2: 1. Age \>=18 years. 2. Pathological criteria: EGFRvIII+ GBM from most recent surgery, confirmed by a Clinical Laboratory Improvement Amendments (CLIA)-certified lab using a next-generation sequencing panel. * Inclusion Criteria for Study Enrollment for Cohort 2 1. Karnofsky Performance Scale (KPS) score \>=70. 2. 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. 3. Pathological criteria: EGFRvIII+ GBM from most recent surgery, as defined by an EGFRvIII H-score of ≥ 150 based on central review. 4. Is surgically amenable, with expectation for ability to resect at least 500 mg of tumor tissue confirmed by participant's neurosurgeon. 5. 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. 6. Females of childbearing potential must have a negative serum beta-human chorionic gonadotropin (HCG) pregnancy test prior to receiving study interventions. 7. All participants must have adequate organ function. a. 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. f. 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) 8. Must be willing to provide voluntary informed consent for study intervention. Exclusion Criteria: * Exclusion Criteria for Cohort 1 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. 2. 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. 3. Known addiction to alcohol or illicit drugs. 4. Prior treatment with any Epithelial Growth Factor Receptor (EGFR)-targeting therapy. 5. Participants with leptomeningeal dissemination. 6. 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. 7. 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. 8. Participants who have received prior solid organ or bone marrow transplantation. 9. 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. 10. Participants who are unable to return for follow-up visits or obtain follow-up studies required to assess toxicity to therapy. * Exclusion Criteria for Tissue Screening for Cohort 2 1\. Participant is unwilling to undergo another surgery if felt clinically appropriate. * Exclusion Criteria for Study Enrollment for Cohort 2 1. Prior treatment with any EGFR-targeting therapy 2. 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. 3. Participants with imaging or clinical evidence of uncontrolled tumor mass effect; the assessment of mass effect will be made by the Investigators. 4. Participants with leptomeningeal dissemination. 5. 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. 6. 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. 7. Participants who have received prior solid organ or bone marrow transplantation. 8. Female participants who are pregnant or breast-feeding. 9. 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. 10. Participants who are unable to return for follow-up visits or obtain follow-up studies required to assess toxicity to therapy.
Contact & Investigator
Jennifer Clarke, MD, MPH
STUDY CHAIR
University of California, San Francisco
Frequently Asked Questions
Who can join the NCT06186401 clinical trial?
This trial is open to participants of all sexes, aged 18 Years or older, studying EGFR Gene Mutation. Full inclusion and exclusion criteria are listed in the Eligibility Criteria section. Always confirm your eligibility with the research team before applying.
What phase is the NCT06186401 trial and what does that mean for participants?
Phase 1 trials are the first stage of human testing. The primary goal is to assess safety and determine appropriate dosage levels. Participants are closely monitored. These trials typically involve a small number of volunteers.
Is NCT06186401 currently recruiting?
Yes, NCT06186401 is actively recruiting participants. Contact the research team at NeuroOncNewPatientCoord@ucsf.edu for enrollment information.
Where is the NCT06186401 trial being conducted?
This trial is being conducted at San Francisco, United States.
Who is sponsoring the NCT06186401 clinical trial?
NCT06186401 is sponsored by Hideho Okada, MD, PhD. The principal investigator is Jennifer Clarke, MD, MPH at University of California, San Francisco. The trial plans to enroll 20 participants.