NCT05168423

Brief Summary

This is an open-label phase 1 study to assess the safety and feasibility of autologous T cells co-expressing two CARs targeting the cryptic EGFR epitope 806 and IL13Ra2 (referred to as "CART-EGFR-IL13Ra2 cells") in patients with EGFR-amplified glioblastoma, IDH-wildtype that has recurred following prior radiotherapy.

Trial Health

75
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
67

participants targeted

Target at P75+ for phase_1

Timeline
165mo left

Started Feb 2023

Longer than P75 for phase_1

Geographic Reach
1 country

1 active site

Status
active not recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Progress20%
Feb 2023Dec 2039

First Submitted

Initial submission to the registry

November 22, 2021

Completed
1 month until next milestone

First Posted

Study publicly available on registry

December 23, 2021

Completed
1.2 years until next milestone

Study Start

First participant enrolled

February 24, 2023

Completed
16.8 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

December 19, 2039

Expected
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

December 19, 2039

Last Updated

April 13, 2026

Status Verified

April 1, 2026

Enrollment Period

16.8 years

First QC Date

November 22, 2021

Last Update Submit

April 6, 2026

Conditions

Glioblastoma

Outcome Measures

Primary Outcomes (5)

  • Number of Subjects with treatment related adverse events using NCI Common Terminology Criteria for Adverse Events (CTCAE) V5.0

    Type, frequency, severity, and attribution of adverse events

    Up to 15 years following CART-EGFR-IL13Ra2 administration

  • Number of subjects with dose-limiting toxicities (DLTs)

    Dose Escalation Phase only; Unacceptable toxicity as defined by the protocol

    28 days following initial treatment with CART-EGFR-IL13Ra2 cells

  • Determination of maximum tolerated dose (MTD).

    Dose Escalation Phase only: The maximum tolerated dose (MTD) is defined as the highest dose explored at which 0 or 1 DLT occurs in 6 evaluable subjects.

    28 days following initial treatment with CART-EGFR-IL13Ra2 cellsnths

  • Determine the recommended dose for expansion (RDE).

    Up to 12 months following initial treatment with CART-EGFR-IL13Ra2 cells

  • Proportion of eligible subjects who receive all planned doses of CART-EGFR-IL13Ra2 cells.

    Cohort 4 only

    28 days following initial treatment with CART-EGFR-IL13Ra2 cells

Secondary Outcomes (6)

  • Proportion of subjects who enroll on this study who received study treatment.

    12 months

  • Frequency of manufacturing failures

    3 months

  • Progression-Free Survival (PFS)

    Up to 15 years following CART-EGFR-IL13Ra2 administration

  • Objective Response Rate (ORR)

    Up to 12 months following CART-EGFR-IL13Ra2 administration

  • Duration of response (DOR)

    Up to 15 years following initial CART-EGFR-IL13Ra2 administration

  • +1 more secondary outcomes

Study Arms (5)

Cohort 1

EXPERIMENTAL

Participants will receive a single fixed dose of 1x10\^7 CART-EGFR-IL13Ra2 cells via intrathecal administration on Day 0.

Drug: CART-EGFR-IL13Ra2 Cells

Cohort -1

EXPERIMENTAL

Participants will receive a single fixed dose of 5x10\^6 CART-EGFR-IL13Ra2 cells via intrathecal administration on Day 0.

Drug: CART-EGFR-IL13Ra2 Cells

Cohort 2

EXPERIMENTAL

Participants will receive a single fixed dose of 2.5x10\^7 CART-EGFR-IL13Ra2 cells via intrathecal administration on Day 0.

Drug: CART-EGFR-IL13Ra2 Cells

Cohort 3

EXPERIMENTAL

Participants will receive a single fixed dose of 5x10\^7 CART-EGFR-IL13Ra2 cells via intrathecal administration on Day 0.

Drug: CART-EGFR-IL13Ra2 Cells

Cohort 4

EXPERIMENTAL

Participants will receive a single dose of 2.5x107 CART-EGFR-IL13Ra2 cells given via intrathecal administration on Day 0, followed by a second dose of 2.5x107 CART-EGFR-IL13Ra2 cells given via intrathecal administration on Day 14 (+/-1d).

Drug: CART-EGFR-IL13Ra2 Cells

Interventions

CART-EGFR-IL13Ra2 CellsDRUG

autologous T cells transduced with a bicistronic lentiviral vector containing a murine scFv targeting EGFR and a humanized scFv targeting IL13Ra2

Cohort -1Cohort 1Cohort 2Cohort 3Cohort 4

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Signed, written informed consent
  • Male or female age ≥ 18 years
  • Patients with glioblastoma, IDH-wildtype (as defined by WHO 2021 Classification of CNS Tumors) that has recurred following prior radiotherapy. For patients with tumors harboring methylation of the MGMT promoter, at least 12 weeks must have elapsed since completion of first-line radiotherapy.
  • Tumor tissue positive for wild-type EGFR amplification by NeoGenomics Laboratories. Archival tumor from patient's initial surgery at time of original diagnosis or recently collected tumor from time of recurrence are acceptable.
  • Surgical tumor resection for disease control/management or tumor biopsy to confirm tumor recurrence is clinically indicated in the opinion of the physician-investigator.
  • Adequate organ function defined as:
  • Serum creatinine ≤ 1.5 x ULN or estimated creatinine clearance ≥ 30 ml/min and not on dialysis.
  • ALT/AST ≤ 3 x upper limit of normal range and total bilirubin ≤ 2.0 mg/dl, except for patients in whom hyperbilirubinemia is attributed to Gilbert's syndrome (≤ 3.0 mg/dl).
  • Left Ventricular Ejection Fraction (LVEF) ≥ 45% confirmed by ECHO/MUGA
  • Must have a minimum level of pulmonary reserve defined as ≤ Grade 1 dyspnea and pulse oxygen \> 92% on room air
  • Karnofsky Performance Status ≥ 60%.
  • Subjects of reproductive potential must agree to use acceptable birth control methods.

You may not qualify if:

  • Active hepatitis B or hepatitis C infection.
  • Any other active, uncontrolled infection.
  • Class III/IV cardiovascular disability according to the New York Heart Association Classification.
  • Tumors primarily localized to the brain stem or spinal cord.
  • Severe, active co-morbidity in the opinion of the physician-investigator that would preclude participation in this study.
  • Receipt of bevacizumab within 3 months prior to physician-investigator confirmation of eligibility.
  • Active autoimmune disease requiring systemic immunosuppressive treatment equivalent to ≥ 10 mg daily of prednisone. Patients with autoimmune neurological diseases (such as MS or Parkinson's) will be excluded.
  • Patients who are pregnant or nursing (lactating).
  • History of allergy or hypersensitivity to study product excipients (human serum albumin, DMSO, and Dextran 40).

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

Related Publications (2)

  • Bagley SJ, Desai AS, Fraietta JA, Silverbush D, Chafamo D, Freeburg NF, Gopikrishna GK, Rech AJ, Nabavizadeh A, Bagley LJ, Park J, Jarocha D, Martins R, Sarmiento N, Maloney E, Lledo L, Stein C, Marshall A, Leskowitz RM, Jadlowsky JK, Mackey S, Christensen S, Oner BS, Plesa G, Brennan A, Gonzalez V, Chen F, Barrett D, Colbourn R, Nasrallah MP, Mourelatos Z, Hwang WT, Alanio C, Siegel DL, June CH, Hexner EO, Binder ZA, O'Rourke DM. Intracerebroventricular bivalent CAR T cells targeting EGFR and IL-13Ralpha2 in recurrent glioblastoma: a phase 1 trial. Nat Med. 2025 Aug;31(8):2778-2787. doi: 10.1038/s41591-025-03745-0. Epub 2025 Jun 1.

    PMID: 40451950DERIVED

  • Bagley SJ, Logun M, Fraietta JA, Wang X, Desai AS, Bagley LJ, Nabavizadeh A, Jarocha D, Martins R, Maloney E, Lledo L, Stein C, Marshall A, Leskowitz R, Jadlowsky JK, Christensen S, Oner BS, Plesa G, Brennan A, Gonzalez V, Chen F, Sun Y, Gladney W, Barrett D, Nasrallah MP, Hwang WT, Ming GL, Song H, Siegel DL, June CH, Hexner EO, Binder ZA, O'Rourke DM. Intrathecal bivalent CAR T cells targeting EGFR and IL13Ralpha2 in recurrent glioblastoma: phase 1 trial interim results. Nat Med. 2024 May;30(5):1320-1329. doi: 10.1038/s41591-024-02893-z. Epub 2024 Mar 13.

    PMID: 38480922DERIVED

MeSH Terms

Conditions

Glioblastoma

Condition Hierarchy (Ancestors)

AstrocytomaGliomaNeoplasms, NeuroepithelialNeuroectodermal TumorsNeoplasms, Germ Cell and EmbryonalNeoplasms by Histologic TypeNeoplasmsNeoplasms, Glandular and EpithelialNeoplasms, Nerve Tissue

Study Officials

  • Stephen Bagley, MD, MSCE

    University of Pennsylvania

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 1
Allocation
NON RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
SEQUENTIAL
Model Details: 3+3 Dose escalation design
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

November 22, 2021

First Posted

December 23, 2021

Study Start

February 24, 2023

Primary Completion (Estimated)

December 19, 2039

Study Completion (Estimated)

December 19, 2039

Last Updated

April 13, 2026

Record last verified: 2026-04

Locations

US(1)