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

Part of paid clinical trials in San Francisco, California.

Sponsor
Hideho Okada, MD, PhD
Study ID
NCT06186401
Phase
PHASE1
Status
Recruiting
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Conditions

Eligibility Criteria

Sex
ALL
Age
18 Years - N/A
Healthy Volunteers
Not accepted

Interventions

  • E-SYNC T Cells — BIOLOGICAL
    Given IV
  • Cyclophosphamide (non-investigational) — DRUG
    Given IV
  • Fludarabine (non-investigational) — DRUG
    Given IV
  • Leukapheresis — PROCEDURE
    Undergo leukapheresis
  • Surgical resection — PROCEDURE
    Undergo surgical resection of tumor tissue

Study Details

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 Dates

Start date
Apr 30, 2024
Status verified
Mar 2026
Primary completion
Dec 31, 2027
Completion
Dec 31, 2027

Study Design

Enrollment
20 participants (estimated)
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT

Arms

  • Experimental: Cohort 1: Starting Dose Level 1 (5 x 10^7 CAR+ cells) (DL1)
    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.
  • Experimental: Cohort 1: Dose-escalation Level 2 (1.5 x 10^8 CAR+ cells) (DL2)
    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.
  • Experimental: Cohort 2: Tissue analysis cohort
    Participants with EGFRvIII+ glioblastoma recurrence after initial non-investigational, chemoradiation who need surgery will have the EGFRvIII H-scored based on digital image analysis of EGFRvIII immunohistochemistry (IHC) slides, with the score denoting both extent of and intensity of positive staining. Participants with an H-score of \>=250 will undergo leukapheresis for manufacturing of E-SYNC T cells at the maximum tolerated dose, or recommended dose based on results from cohort 1 more than 2 weeks after completion of their non-investigational, standard of care radiation therapy. Participants will receive a single infusion of drug product (DP) on day 0 and will be admitted to the hospital for surgical resection (non-investigational) between days 14 and 28, and monitored for safety, presence of and possible synNotch \> CAR-T priming of the DP in the peripheral blood, and anti-tumor response of E-SYNC T cells.

Primary Outcome Measure

Proportion of participants reporting treatment-emergent adverse events [ Time Frame: Up to 96 weeks ]

Central Contacts

Locations (1)

FacilityCityStateZIPSite coordinators
University of California, San FranciscoSan FranciscoCalifornia94143
Neuro-Oncology New Patient Coordinator
[email protected]
877-827-3222
[email protected]
Jennifer Clarke, MD, MPH (PRINCIPAL_INVESTIGATOR)
Hideho Okada, MD, PhD (SUB_INVESTIGATOR)

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By condition
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By specialty
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By research site
University of California, San Francisco· San Francisco, CA

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