Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Class |
|---|---|
| Kite Pharma (a Gilead Company) | UNKNOWN |
Not provided
Not provided
Not provided
Not provided
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.
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Cohort 1 | Experimental | Participants will receive a single fixed dose of 1x10^7 CART-EGFR-IL13Ra2 cells via intrathecal administration on Day 0. |
|
| Cohort -1 | Experimental | Participants will receive a single fixed dose of 5x10^6 CART-EGFR-IL13Ra2 cells via intrathecal administration on Day 0. |
|
| Cohort 2 | Experimental | Participants will receive a single fixed dose of 2.5x10^7 CART-EGFR-IL13Ra2 cells via intrathecal administration on Day 0. |
|
| Cohort 3 | Experimental | Participants will receive a single fixed dose of 5x10^7 CART-EGFR-IL13Ra2 cells via intrathecal administration on Day 0. |
|
| 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). |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| CART-EGFR-IL13Ra2 Cells | Drug | autologous T cells transduced with a bicistronic lentiviral vector containing a murine scFv targeting EGFR and a humanized scFv targeting IL13Ra2 |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| Proportion of subjects who enroll on this study who received study treatment. | Evaluated based on the proportion of subjects who screen fail and those who receive any dose of CART-EGFR-IL13Ra2 cells. | 12 months |
| Frequency of manufacturing failures |
Not provided
Inclusion Criteria:
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:
Karnofsky Performance Status ≥ 60%.
Subjects of reproductive potential must agree to use acceptable birth control methods.
Exclusion Criteria:
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Affiliation | Role |
|---|---|---|
| Stephen Bagley, MD, MSCE | University of Pennsylvania | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Pennsylvania | Philadelphia | Pennsylvania | 19104 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 42296961 | Derived | Freeburg NF, Chafamo D, Konanur Gopikrishna G, Murphy RM, Peng JJ, Parthasarathy S, Dumont S, Estrada EG, Logun MT, Sun Y, Wang X, Grover P, Rodriguez JL, Zhang DL, Park K, Fu Y, Ben Hamouda N, Hernandez-Verdin I, Lamrani L, Hicks KA, Cooper NA, Ekwegbara C, Bawden EG, Waterfall JJ, Fuentealba J, Alcantara M, Seykora JT, Prouty SM, Barrett D, Banerjee E, Cox A, Assenmacher CA, Macia C, Yin M, Carpenter EL, Ming GL, Sautes-Fridman C, Fridman WH, Tartour E, Wherry EJ, Amigorena S, Fraietta JA, Nasrallah MP, Song H, Miller TE, Bagley SJ, O'Rourke DM, Binder ZA, Alanio C, Silverbush D. The critical role of the endogenous immune compartment after CAR T cell therapy in recurrent GBM. Cell. 2026 Jun 15:S0092-8674(26)00585-4. doi: 10.1016/j.cell.2026.05.026. Online ahead of print. | |
| 40451950 |
Not provided
Not provided
Not provided
| ID | Term |
|---|---|
| D005909 | Glioblastoma |
| ID | Term |
|---|---|
| D001254 | Astrocytoma |
| D005910 | Glioma |
| D018302 | Neoplasms, Neuroepithelial |
| D017599 | Neuroectodermal Tumors |
Not provided
Not provided
3+3 Dose escalation design
Not provided
Not provided
Not provided
Not provided
Proportion of subjects with CART-EGFR-IL13Ra2 products that fail to meet the product release criteria, out of the number of subjects in whom manufacturing was attempted.
Proportion of subjects with CART-EGFR-IL13Ra2 products that fail to meet the assigned dose, out of the number of subjects in whom manufacturing was attempted.
| 3 months |
| Progression-Free Survival (PFS) | Per modified RANO criteria | Up to 15 years following CART-EGFR-IL13Ra2 administration |
| Objective Response Rate (ORR) | Per modified RANO criteria (in subjects with measurable disease at the time of study treatment); Proportion of subjects with confirmed CR and PR. | Up to 12 months following CART-EGFR-IL13Ra2 administration |
| Duration of response (DOR) | Per modified RANO criteria (in subjects with measurable disease at the time of study treatment); Time from the date when a response of confirmed CR/PR is first met to the date of confirmed disease progression, death or receipt of alternative treatment other than CART-EGFR-IL13Ra2 retreatment. | Up to 15 years following initial CART-EGFR-IL13Ra2 administration |
| Overall Survival (OS) | Time from initial study treatment to the date of death from any cause. | Up to 15 years following initial CART-EGFR-IL13Ra2 administration |
| Derived |
| 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. |
| 38480922 | Derived | 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. |
| D009373 |
| Neoplasms, Germ Cell and Embryonal |
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
| D009375 | Neoplasms, Glandular and Epithelial |
| D009380 | Neoplasms, Nerve Tissue |