Relapsed/refractory glioblastoma Cancer
Conditions
Interventions
Whilst the CARGO-T cells are being manufactured, bridging therapy will be given to maintain disease control which may include proton beam therapy.
Following a lymphodepleting regimen of fludarabine &
Sponsors
University College London
Eligibility
Sex/Gender
All
Age
16 Years to 99 Years
Inclusion criteria
Inclusion criteria: 1. Age =16 years 2. Disease status: 2.1. Relapsed or recurrent IDH-wildtype GBM confirmed by pathology review of surgically resected tissue, and 2.2. Tumour tissue is positive for EGFRvIII expression as performed by immunohistochemistry (IHC) 3. Written informed consent (or where applicable, consent by a legal representative) 4. Agree to undergo a pregnancy test and use adequate contraception (where applicable) Trial inclusion criteria: for radiotherapy: 5. =6 months since completion of primary radiotherapy. 6. Prior history of standard dose, conventionally fractionated brain radiotherapy (i.e. 54 - 60Gy in 28 - 33 fractions). 7. Up to and including three enhancing lesions. 8. Predicted re-irradiation Gross Tumour Volume <50cm³ 9. Maximum diameter of enhancing disease must be =6cm
Exclusion criteria
Exclusion criteria: Current key exclusion criteria as of 20/01/2026: 1. ECOG 3 - 4 2. Metastatic or primary spinal GBM 3. Organ function: 3.1. Cardiac: Serious and uncontrolled cardiac arrhythmias despite medical management, history of ischemic heart disease within the last 6 months before eligibility confirmation and left ventricular ejection fraction (LVEF) 2x upper limit of normal 3.5. Neurologic: Pre-existing significant neurological disorders unrelated to the CNS malignancy investigated in this study 4. Active hepatitis B, C or HIV 5. Active severe infection 6. History of or active medical or psychiatric condition that is uncontrolled with current treatment or deemed by the investigators to be severe enough to preclude participation in this study 7. Unable to undergo leukapheresis due to contraindications, inability to tolerate procedure and/or issues with adequate venous access for the procedure 8. Known allergy to study product excipients (albumin, DMSO, dextran) 9. Cohort 3 only: Any contraindications to receiving ipilimumab including history of clinically significant pneumonitis or lung fibrosis 4 mg dexamethasone (or equivalent) daily 12. Women who are pregnant or breastfeeding _____ Previous key exclusion criteria: 1. ECOG 3 - 4 2. Metastatic or primary spinal GBM 3. Organ function: 3.1. Cardiac: Serious and uncontrolled cardiac arrhythmias despite medical management, history of ischemic heart disease within the last 6 months before eligibility confirmation and left ventricular ejection fraction (LVEF) 2x upper limit of normal 3.5. Neurologic: Pre-existing significant neurological disorders unrelated to the CNS malignancy investigated in this study 4. Active hepatitis B, C or HIV 5. Active severe infection 6. History of or active medical or psychiatric condition that is uncontrolled with current treatment or deemed by the investigators to be severe enough to preclude participation in this study 7. Unable to undergo leukapheresis due to contraindications, inability to tolerate procedure and/or issues with adequate venous access for the procedure 8. Known allergy to study product excipients (albumin, DMSO, dextran) 9. Cohort 3 only: Any contraindications to receiving ipilimumab including history of clinically significant pneumonitis or lung fibrosis 2 mg dexamethasone (or equivalent) daily 12. Women who are pregnant or breastfeeding
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 1. Toxicity following CARGO-T cells administration will be evaluated by the number of grade 3-5 adverse events causally related to the ATIMP at 28 days post ATIMP infusion 2. Feasibility of leukapheresis collection and generation of CARGO-T cells as evaluated by the number of therapeutic products generated following ATIMP manufacture 3. Feasibility of administration of CARGO-T cells therapy measured by the number of successful CARGO-T cells administrations, firstly as an IV agent (Theme 1) and in the event of non-response/relapse following IV, as an ICV agent, with option for repeated dosing (Theme 2) | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. Efficacy will be measured by the proportion of patients achieving responses and depth of response following the RANO 2.0 criteria at 1, 3 and 6 months post ATIMP infusion 2. Persistence and frequency of circulating CARGO-T cells in peripheral blood will be assessed by the number of CARGO-T cells in blood samples as per flow cytometry and qPCR at several timepoints between ATIMP infusion to 24 months post infusion 3. Relapse rate, progression-free survival and overall survival will be assessed at 12 and 24 months post ATIMP infusion 4. The feasibility of proton beam therapy as a bridging therapy will be assessed by the proportion of patients who complete PBT as planned at the time of completion of PBT, and the proportion of patients who then undergo CARGO-T cells administration on Day 0 (infusion) | — |
Countries
England, United Kingdom
Outcome results
None listed