Glioblastoma MultiformePhase 1NCT05366179
Autologous CAR-T Cells Targeting B7-H3 in Recurrent or Refractory GBM CAR.B7-H3Tc
A Phase 1 study testing CAR.B7-H3T cells infusion in people with Glioblastoma Multiforme, run by UNC Lineberger Comprehensive Cancer Center at 1 site in United States.
Trial summary
The purpose of this study is to test the safety of using T lymphocyte chimeric antigen receptor cells against the B7-H3 antigen (CAR.B7-H3T cells) in patients with glioblastoma. CAR.B7-H3T cells treatment has not been tested in humans and is not an approved treatment by the Food and Drug Administration for… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Glioblastoma Multiforme
- What is being tested?
- CAR.B7-H3T cells infusion
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 36 participants
- Where
- 1 siteUnited States
- Study dates
- 2 Sep 2022to 30 May 2030
- Phase
- Phase 1
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Karnofsky score of > 60%
- Diagnosis or recurrent supratentorial- or infra-tentorial glioblastoma multiforme (GBM) (World Health Organization 2016 or 2021) based on Response assessment in neuro-oncology criteria (RANO) magnetic resonance imaging (MRI) criteria. Disseminated GBM down the spinal cord is not allowed. Must have previously undergone resection or biopsy at initial diagnosis.
- Must have undergone at least 4005 cGy of radiation with concurrent temozolomide.
- No current or previous exposure to antiangiogenic agents, such as bevacizumab.
- Female subjects of childbearing potential must be willing to abstain from heterosexual activity or to use 2 forms of effective methods of contraception from the time of informed consent until 6 months after study treatment discontinuation.
- Male subjects with female partners must have had a prior vasectomy or agree to use an adequate method of contraception starting with the first dose of study therapy through 3 months after the cell infusion therapy. If a male subject receives multiple infusions, they must remain on contraception throughout the duration and 3 months after the last cell infusion therapy.
- The subject is willing and able to comply with study procedures based on the judgment of the investigator.
Who cannot join
- Subject is pregnant or lactating (Note: Breast milk cannot be stored for future use while the mother is being treated on study).
- Subjects with a prior or concurrent malignancy whose natural history or treatment has the potential to interfere with the safety or efficacy assessment of the investigational regimen.
- Active infection with HIV, hepatitis B virus, hepatitis C virus (HCV). Note: To meet eligibility subjects are required to be negative for HIV antibody, negative for HTLV1 and 2 antibodies, negative for Hepatitis B surface antigen, and negative for HCV antibody and viral load.
- Contraindication to MRI contrast agents or an inability to undergo MRI scans due to MRI non-compatible implanted materials.
- Prior exposure to chimeric antigen receptor T cell therapy for treatment of glioblastoma.
- Evidence of disseminated disease involving the brainstem, cerebellum or spinal cord.
- Previously implanted carmustine wafers or brachytherapy for the treatment of glioma.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
Lineberger Comprehensive Cancer Center
Chapel Hill, North Carolina, 27599
Sierra Thomas, 919-445-4208, UNCImmunotherapy@med.unc.edu
Chelsea Baker, +1 919-962-8491, UNCImmunotherapy@med.unc.edu
About this study
Official title: Phase I Study of Intraventricular Infusion of T Cells Expressing B7-H3 Specific Chimeric Antigen Receptors (CAR) in Subjects With Recurrent or Refractory Glioblastoma
The purpose of this study is to test the safety of using T lymphocyte chimeric antigen receptor cells against the B7-H3 antigen (CAR.B7-H3T cells) in patients with glioblastoma. CAR.B7-H3T cells treatment has not been tested in humans and is not an approved treatment by the Food and Drug Administration for glioblastoma.
Read the detailed description
This is a phase 1, single center, open-label study aims to determine the safety of escalating doses of chimeric antigen receptor T cells (CAR-T) cells targeting the B7-H3 antigen administered via intraventricular infusion to adult subjects with relapsed or refractory glioblastoma (GBM).
Subjects with GBM who meet procurement eligibility criteria will have cells collected following their initial surgical resection to manufacture CAR.B7-H3T cells, preferably prior to initiation of adjuvant chemoradiation.
At the time that the subjects have confirmed refractory or recurrent GBM, CAR.B7-H3T cells will be manufactured for subjects who likely to be eligible for cell infusion.
Eligible subjects will receive up to 3 weekly infusions of CAR.B7-H3 cells. To receive the additional cycles of CAR.B7-H3 cells, all treatment-related toxicities must have resolved to grade < 3, the subject must not have experienced a dose limiting toxicity (DLT) and the subject must not have progressive disease that has been confirmed by magnetic resonance imaging per Immunotherapy response assessment in neuro-oncology criteria.
The data from the dose escalation will be used to determine a recommended phase 2 dose (RP2D), which will be decided on based on the maximum tolerated dose (MTD) and additional factors such as the feasibility of administering infusions.
- Conditions
- Glioblastoma Multiforme
- Being tested
- CAR.B7-H3T cells infusion
- Keywords
- Brain Tumor, Glioblastoma Multiforme, Cell therapy, Relapse, Recurrent
- Medical subject headings
- Glioblastoma, Brain Neoplasms, Recurrence
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CAR.B7-H3T cells infusionDrug
The Chimeric Antigen Receptors (CAR).B7-H3T cells will be administered via intraventricular infusion up to 3 weekly infusions. A suspension of T cells infusion is given, over 5-10 minutes, via a Rickham catheter and will be followed by a normal-saline flush.
Dose escalation will be performed considering the dose limiting toxicities (DLTs) listed in the protocol. Six doses will be explored. The starting dose will be 2 × 10^6 transduced cells/infusion (Dose Level (DL) 1) and will enroll at least 3 subjects. If there are no dose DLTs within 4 weeks of the third cellular product administration in the first 3 subjects, then the next cohort will evaluate 5 × 10^6 transduced cells/infusion (DL2).
| Study group | Role | What they receive |
|---|---|---|
| Single Arm | Experimental | CAR.B7-H3 T cells:
Subjects with refractory or recurrent glioblastoma multiforme, have cells collected following their initial surgical resection to manufacture CAR.B7-H3 T cells, preferably before initiation of adjuvant chemoradiation. Receives: Drug: CAR.B7-H3T cells infusion |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of participants with adverse event
Number of participants with adverse event (AE)s as a measure of safety and tolerability of intraventricular administration CAR.B7-H3 T cells in subjects with progressive recurrent or refractory glioblastoma multiforme.
AEs will be classified and graded according to the National Cancer Institute's Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 5.0. Dose Limiting Toxicities (DLTs) are defined as at least possibly related to CAR.B7-H3T cell product administration.
Measured: Up to 10 weeks
Cytokine Release Syndrome
Cytokine Release Syndrome (CRS) will be graded according to American Society for Transplantation and Cellular Therapy (ASTCT) CRS Consensus Grading.
Grade 1 - Mild (Symptomatic Management): Fever ≥38^ o C, No hypotension, No hypoxia, Grade 2 - Moderate (Moderate Intervention): Fever ≥38^ o C, Hypotension not requiring vasopressors, Hypoxia requiring low-flow nasal cannula (≤6 L/minute) or blow-by, Grade 3 - Severe (Aggressive Intervention): Fever ≥ 38^ o C , Hypotension requiring a vasopressor with or without vasopressin, Hypoxia requiring high-flow nasal cannula (>6 L/minute), facemask, nonrebreather mask, or Venturi mask, Grade 4 - Life-threatening (Life-sustaining intervention): Fever ≥38^oC, Hypotension requiring multiple vasopressors (excluding vasopressin),Hypoxia requiring positive pressure (e.g. Continuous positive airway pressure, BiPAP, intubation, mechanical ventilation), Grade 5 - Death: Death.
Measured: Up to 10 weeks
Neurotoxicity
Neurotoxicity will be graded according to the Central Nervous System (CNS) Toxicity criteria.
Grade 0: Normal or no change from baseline exam at start of therapy, Grade 1: Mild lethargy and/or irritability or visual, motor, or sensory symptoms without change in neurological exam, Grade 2: Moderate lethargy, disorientation, or psychosis lasting < 48 hours or mild increase in pre-existing neurological deficit, Grade 3: >48hours of severe lethargy, but responsive to verbal stimuli or disorientation or psychosis lasting >48 hours, Grade 4: Coma, unresponsive to verbal stimuli, increasing neurological deficit above grade 3, evidence of herniation, development of uncontrolled seizures, intracerebral hemorrhage.
Measured: Up to 10 weeks
Secondary outcomes (5)
Identification of Recommended phase 2 dose (RP2D)
RP2D for intraventricular administration of CAR.B7-H3 T cells is determined based on the modified 3+3 dose-finding rule. Dose escalation will be performed considering the dose-limiting toxicities (DLTs), dose level (DL) will be increased unless there is no DLT.
Measured: Up to 4 weeks
Objective Response Rate (ORR)
ORR is defined as the percentage of subjects with [compete response (CR) + partial response (PR) + stable disease] per Immunotherapy response assessment in neuro-oncology (iRANO) criteria.
Complete response (CR): Disappearance of all enhancing disease for ≥ 4 weeks; no new lesions; stable or improved T2-weighted-fluid-attenuated inversion recovery (T2/FLAIR); no more than physiological steroids; clinically stable or improved.
Partial response (PR): ≥ 50% decrease in the sum of biperpendicular diameters of enhancing disease for ≥ 4 weeks; no new lesions; stable or improved T2/FLAIR; stable or decreased steroid dose, clinically stable or improved.
Stable disease (SD): Does not qualify for CR, PR or progressive disease; no new lesions; stable or improved T2/FLAIR; stable or decreased steroid dose; clinically stable or improved.
Measured: Up to 4 weeks
Progression Free Survival (PFS)
PFS is defined as the time from with the initial CAR.B7-H3 T cell infusion until disease progression per iRANO criteria or death as a result of any cause. Subjects who do not meet criteria for progression by the analysis cut-off date will be censored at their last evaluable disease assessment date.
Immunotherapy response assessment in neuro-oncology (iRANO) criteria.
Progressive disease (PD): ≥ 25% increase in the sum of biperpendicular diameters of enhancing disease; or new lesions; or substantial worsened T2/FLAIR; or substantial clinical decline.
Measured: Up to 12 months
Overall Survival (OS)
OS is defined as the time from initial glioblastoma multiforme diagnosis to date of death for any cause.
Measured: Up to 5 years
Duration of Response (DOR)
DOR is defined as the time from documentation of PR or better to progressive disease (PD).
Measured: Up to 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 May 2022
- Study start2 Sep 2022
- Primary completion30 May 2030 (estimated)
- Study completion30 May 2030 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Glioblastoma MultiformeStudies of the same condition, open and under way.
- More trials run by UNC Lineberger Comprehensive Cancer CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 36 participants (estimated)
Sponsor and investigators
- Lead sponsor
- UNC Lineberger Comprehensive Cancer Center
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Felicia Cao, MD, PhD, Principal investigator, UNC Lineberger Comprehensive Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05366179
- Sponsor's protocol ID
- LCCC2059-ATL
- Status last verified
- Apr 2026
- First submitted
- 4 May 2022
- Last updated
- 22 Apr 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 22 Apr 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I Study of Intraventricular Infusion of T Cells Expressing B7-H3 Specific Chimeric Antigen Receptors (CAR) in Subjects With Recurrent or Refractory Glioblastoma
- ClinicalTrials.gov ID
- NCT05366179
- Acronym / sponsor ID
- LCCC2059-ATL
- Conditions
- Glioblastoma Multiforme
- Keywords
- Brain Tumor, Glioblastoma Multiforme, Cell therapy, Relapse, Recurrent
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 36 participants (estimated)
- Lead sponsor
- UNC Lineberger Comprehensive Cancer CenterUniversity, hospital or other
- Study start
- 2 Sep 2022 (actual)
- Primary completion
- 30 May 2030 (estimated)
- Study completion
- 30 May 2030 (estimated)
- First posted
- 9 May 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to test the safety of using T lymphocyte chimeric antigen receptor cells against the B7-H3 antigen (CAR.B7-H3T cells) in patients with glioblastoma. CAR.B7-H3T cells treatment has not been tested in humans and is not an approved treatment by the Food and Drug Administration for glioblastoma.
Detailed description
This is a phase 1, single center, open-label study aims to determine the safety of escalating doses of chimeric antigen receptor T cells (CAR-T) cells targeting the B7-H3 antigen administered via intraventricular infusion to adult subjects with relapsed or refractory glioblastoma (GBM).
Subjects with GBM who meet procurement eligibility criteria will have cells collected following their initial surgical resection to manufacture CAR.B7-H3T cells, preferably prior to initiation of adjuvant chemoradiation.
At the time that the subjects have confirmed refractory or recurrent GBM, CAR.B7-H3T cells will be manufactured for subjects who likely to be eligible for cell infusion.
Eligible subjects will receive up to 3 weekly infusions of CAR.B7-H3 cells. To receive the additional cycles of CAR.B7-H3 cells, all treatment-related toxicities must have resolved to grade < 3, the subject must not have experienced a dose limiting toxicity (DLT) and the subject must not have progressive disease that has been confirmed by magnetic resonance imaging per Immunotherapy response assessment in neuro-oncology criteria.
The data from the dose escalation will be used to determine a recommended phase 2 dose (RP2D), which will be decided on based on the maximum tolerated dose (MTD) and additional factors such as the feasibility of administering infusions.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Single Arm | Experimental | Drug: CAR.B7-H3T cells infusionCAR.B7-H3 T cells: Subjects with refractory or recurrent glioblastoma multiforme, have cells collected following their initial surgical resection to manufacture CAR.B7-H3 T cells, preferably before initiation of adjuvant chemoradiation. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Karnofsky score of > 60%
- Diagnosis or recurrent supratentorial- or infra-tentorial glioblastoma multiforme (GBM) (World Health Organization 2016 or 2021) based on Response assessment in neuro-oncology criteria (RANO) magnetic resonance imaging (MRI) criteria. Disseminated GBM down the spinal cord is not allowed. Must have previously undergone resection or biopsy at initial diagnosis.
- Must have undergone at least 4005 cGy of radiation with concurrent temozolomide.
- No current or previous exposure to antiangiogenic agents, such as bevacizumab.
- Female subjects of childbearing potential must be willing to abstain from heterosexual activity or to use 2 forms of effective methods of contraception from the time of informed consent until 6 months after study treatment discontinuation.
Key exclusion criteria (7 listed)
- Subject is pregnant or lactating (Note: Breast milk cannot be stored for future use while the mother is being treated on study).
- Subjects with a prior or concurrent malignancy whose natural history or treatment has the potential to interfere with the safety or efficacy assessment of the investigational regimen.
- Active infection with HIV, hepatitis B virus, hepatitis C virus (HCV). Note: To meet eligibility subjects are required to be negative for HIV antibody, negative for HTLV1 and 2 antibodies, negative for Hepatitis B surface antigen, and negative for HCV antibody and viral load.
- Contraindication to MRI contrast agents or an inability to undergo MRI scans due to MRI non-compatible implanted materials.
- Prior exposure to chimeric antigen receptor T cell therapy for treatment of glioblastoma.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| CAR.B7-H3T cells infusionThe Chimeric Antigen Receptors (CAR).B7-H3T cells will be administered via intraventricular infusion up to 3 weekly infusions. A suspension of T cells infusion is given, over 5-10 minutes, via a Rickham catheter and will be followed by a normal-saline flush. Dose escalation will be performed considering the dose limiting toxicities (DLTs) listed in the protocol. Six doses will be explored. The starting dose will be 2 × 10^6 transduced cells/infusion (Dose Level (DL) 1) and will enroll at least 3 subjects. If there are no dose DLTs within 4 weeks of the third cellular product administration in the first 3 subjects, then the next cohort will evaluate 5 × 10^6 transduced cells/infusion (DL2). | Drug | Single Arm |
Primary outcome
Number of participants with adverse event
Time frame: Up to 10 weeks
Number of participants with adverse event (AE)s as a measure of safety and tolerability of intraventricular administration CAR.B7-H3 T cells in subjects with progressive recurrent or refractory glioblastoma multiforme. AEs will be classified and graded according to the National Cancer Institute's Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 5.0. Dose Limiting Toxicities (DLTs) are defined as at least possibly related to CAR.B7-H3T cell product administration.
Cytokine Release Syndrome
Time frame: Up to 10 weeks
Cytokine Release Syndrome (CRS) will be graded according to American Society for Transplantation and Cellular Therapy (ASTCT) CRS Consensus Grading. Grade 1 - Mild (Symptomatic Management): Fever ≥38^ o C, No hypotension, No hypoxia, Grade 2 - Moderate (Moderate Intervention): Fever ≥38^ o C, Hypotension not requiring vasopressors, Hypoxia requiring low-flow nasal cannula (≤6 L/minute) or blow-by, Grade 3 - Severe (Aggressive Intervention): Fever ≥ 38^ o C , Hypotension requiring a vasopressor with or without vasopressin, Hypoxia requiring high-flow nasal cannula (>6 L/minute), facemask, nonrebreather mask, or Venturi mask, Grade 4 - Life-threatening (Life-sustaining intervention): Fever ≥38^oC, Hypotension requiring multiple vasopressors (excluding vasopressin),Hypoxia requiring positive pressure (e.g. Continuous positive airway pressure, BiPAP, intubation, mechanical ventilation), Grade 5 - Death: Death.
Neurotoxicity
Time frame: Up to 10 weeks
Neurotoxicity will be graded according to the Central Nervous System (CNS) Toxicity criteria. Grade 0: Normal or no change from baseline exam at start of therapy, Grade 1: Mild lethargy and/or irritability or visual, motor, or sensory symptoms without change in neurological exam, Grade 2: Moderate lethargy, disorientation, or psychosis lasting < 48 hours or mild increase in pre-existing neurological deficit, Grade 3: >48hours of severe lethargy, but responsive to verbal stimuli or disorientation or psychosis lasting >48 hours, Grade 4: Coma, unresponsive to verbal stimuli, increasing neurological deficit above grade 3, evidence of herniation, development of uncontrolled seizures, intracerebral hemorrhage.
5 secondary outcomes
Identification of Recommended phase 2 dose (RP2D)
Time frame: Up to 4 weeks
Objective Response Rate (ORR)
Time frame: Up to 4 weeks
Progression Free Survival (PFS)
Time frame: Up to 12 months
Overall Survival (OS)
Time frame: Up to 5 years
Duration of Response (DOR)
Time frame: Up to 12 months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Apr 2026.
- University of North Carolina Lineberger Comprehensive Cancer Center Clinical TrialsLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Felicia Cao, MD, PhD principal investigator
UNC Lineberger Comprehensive Cancer Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing CAR.B7-H3T cells infusion in people with Glioblastoma Multiforme, run by UNC Lineberger Comprehensive Cancer Center at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 22 Apr 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Catherine Cheng (919-445-4208, UNCImmunotherapy@med.unc.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of participants with adverse event (time frame: Up to 10 weeks). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Apr 2026.