GlioblastomaPhase 1CAR2BRAINNCT03383978
Intracranial Injection of NK-92/5.28.z Cells in Combination With Intravenous Ezabenlimab in Patients With Recurrent HER2-positive Glioblastoma
A Phase 1 study testing NK-92/5.28.z and Ezabenlimab in people with Glioblastoma, run by Johann Wolfgang Goethe University Hospital at 5 sites in Germany.
Trial summary
The main objective of this clinical study is to evaluate the safety and tolerability of NK-92/5.28.z and to determine the maximum tolerated dose or maximum feasible dose (MFD). Recommended phase 2 doses both for intraoperative injections only (RP2Diio) and repetitive injections (RP2Dri) will be determined. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Glioblastoma
- What is being tested?
- NK-92/5.28.z and Ezabenlimab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 42 participants
- Where
- 5 sitesGermany
- Study dates
- 1 Dec 2017to 30 Jun 2028
- 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
- Recurrent or refractory HER2-positive glioblastoma or its variant gliosarcoma in which relapse surgery (partial or total) or a biopsy (biopsy only for the "CAR2BRAIN-CheckR" cohort) is being planned. Those patients with planned biopsy may be included into the "CAR2BRAIN-CheckR" cohort, if all of the following conditions apply:
- Biopsy is necessary (as determined by the treating physician) to rule out the differential diagnosis of pseudoprogression prior to relapse surgery.
- Patients must be candidates for relapse surgery, which must be postponable for four weeks.
- Prior therapy must include the standard of care for glioblastoma (radiotherapy and alkylating chemotherapy, or at least a part thereof if the therapy was terminated prematurely due to therapy failure or poor tolerance). For patients with non-methylated MGMT-Promotor, prior alkylating chemotherapy is dispensable.
- Age ≥ 18 years
- Life expectancy ≥ 3 months
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- Bilirubin ≤ 3x normal, AST ≤ 5x normal, ALT ≤ 5x normal, serum creatinine ≤ 2x upper limit of normal for age, leukocyte count ≥ 3/nl, thrombocyte count ≥ 100/nl and Hb ≥ 8.0 g/dl
- Blood oxygenation of ≥ 90% as measured by pulse oximetry on room air
- Women must have a negative serum pregnancy test within 72h prior to the start of the first NK-92/5.28.z cell injection.
- Sexually active patients must be willing to utilize effective birth control methods throughout the study and for 24 weeks after the last NK-92/5.28.z cell injection. This includes two different forms of effective contraception (e.g. hormonal contraceptive and condom, IUD/IUS and condom) or sterilization.
- Patients should have been off other antineoplastic therapy for two weeks prior to entry in this study. Temozolomide will be allowed up to 48h preinjection. At the time of inclusion, dexamethasone up to a total dose of 4 mg per day will be allowed if medically indicated.
- Informed consent explained to and signed by patient; patient given copy of informed consent.
- Karnofsky performance score of ≥ 70%
Who cannot join
- Anti-angiogenic therapy e.g. with bevacizumab in the last four weeks prior to study entry
- Previous anti-PD-1 or anti-PD-L1 directed checkpoint inhibitor therapy (only "CAR2BRAIN-Check" cohort)
- Coagulation disorder (INR>1.4 or PTT>50sec) or anticoagulation in therapeutic dosage
- History of autoimmune disease, including but not limited to myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, vascular thrombosis associated with antiphospholipid syndrome, Wegener's granulomatosis, Sjögren's syndrome, Guillain-Barré syndrome, multiple sclerosis, vasculitis, or glomerulonephritis. However, patients with a history of autoimmune-related hypothyroidism on a stable dose of thyroid replacement hormone may be eligible for this study.
- Patients with Type I diabetes mellitus not on a stable dose of insulin regimen
- Psoriatic arthritis (however, patients with eczema, psoriasis, lichen simplex chronicus, or vitiligo with dermatologic manifestations only are permitted provided that they meet all of the following conditions:
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- Rash must cover less than 10% of body surface area
- Disease is well controlled at baseline and only requiring low potency topical steroids
- No acute exacerbations of underlying condition within the previous 12 months (not requiring psoralen plus ultraviolet A radiation, methotrexate, retinoids, biologic agents, oral calcineurin inhibitors, high potency or oral steroids))
- Patients with clinical or laboratory signs for immunodeficiency or under immunosuppressive medication other than corticosteroids
- Severe intercurrent infection
- Known HIV, HBV (defined by detection of HBsAg) or HCV positivity (defined by detection of HCV-IgG)
- Chronic heart failure NYHA ≥III
- Patients with a prior solid organ transplantation or allogenic haematopoietic stem cell transplantation
- Patients unable to undergo MRI
- Pregnancy or breastfeeding
- Drug or alcohol abuse
- Severe psychiatric disorder which might interfere with the study treatment or examination
- Simultaneous participation in another interventional clinical trial. If a subject participated in a trial testing another IMP, such IMP should have been terminated at least 30 days before inclusion of the subject.
Trial locations and contacts
5 sites in 1 country. Contact the study team or a site near you to ask about taking part.
5 sites in 1 country
Germany5 sites, 5 recruiting
- Recruiting
Johann W. Goethe University Hospital, Department of Neurosurgery
Frankfurt, 60590
Marie-Therese Forster, Prof. Dr. med., 0049696301 ext. 84488, Marie-Therese.Forster@unimedizin-ffm.de
- Recruiting
Johann W. Goethe University Hospital, Senckenberg Institute of Neurooncology
Frankfurt, 60590
Michael C Burger, PD Dr. med., 0049696301 ext. 84488, michael.burger@unimedizin-ffm.de
Joachim P Steinbach, Prof. Dr. med., 0049696301 ext. 84488, joachim.steinbach@med.uni-frankfurt.de
- Recruiting
Neurochirurgische Klinik, Universitätsklinikum Heidelberg
Heidelberg, Baden-Wurttemberg, 69120
Sandro Krieg, Prof. Dr., Mehtap.Aykac@med.uni-heidelberg.de
- Recruiting
Neurochirurgische Klinik, Universitätsmedizin Mainz
Mainz, Rhineland-Palatinate, 55131
Jens Conrad, Dr., 0049613117 ext. 7331, uct-noz@unimedizin-mainz.de
- Recruiting
Neurochirurgische Klinik, Universitätsmedizin Mannheim
Mannheim, Baden-Wurttemberg, 68167
Miriam Ratliff, Dr., 0049621383 ext. 2750, miriam.ratliff@umm.de
About this study
Official title: Multicenter, Open Label, Phase I Study of Intracranial Injection of NK-92/5.28.z Cells in Patients With Recurrent HER2-positive Glioblastoma
The main objective of this clinical study is to evaluate the safety and tolerability of NK-92/5.28.z and to determine the maximum tolerated dose or maximum feasible dose (MFD). Recommended phase 2 doses both for intraoperative injections only (RP2Diio) and repetitive injections (RP2Dri) will be determined. Frequent side effects and target organs of toxicity and their severity, duration and reversibility will be determined. Furthermore, pharmacokinetics and pharmacodynamics will be examined. In addition, potential signs of anti-tumor activity of NK-92/5.28.z cells will be analyzed. In the separate "CAR2BRAIN-Check" and "CAR2BRAIN-CheckR" cohorts, combination therapy of NK-92/5.28.z with the anti-PD-1 antibody Ezabenlimab (BI 754091) will be tested.
- Conditions
- Glioblastoma
- Being tested
- NK-92/5.28.z, Ezabenlimab
- Medical subject headings
- Glioblastoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
NK-92/5.28.zBiological
Intracranial application of NK-92/5.28.z, 1x10E7-1x10E8
EzabenlimabDrug
Intravenous infusion of Ezabenlimab 240mg q 3 weeks
| Study group | Role | What they receive |
|---|---|---|
| NK-92/5.28.z + Ezabenlimab | Experimental | Intracranial application of NK-92/5.28.z, 1x10E7-1x10E8; intravenous infusion of Ezabenlimab 240mg q 3 weeks Receives: Biological: NK-92/5.28.z; Drug: Ezabenlimab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of participants with treatment-related adverse events as assessed by CTCAE v4.03.
Measured: 24 weeks
Maximum tolerated dose (MTD) or maximum feasible dose (MFD) for NK-92/5.28.z
Measured: 24 weeks
Period of detectability of NK-92/5.28.z cells in blood and cerebrospinal fluid (CSF) during the first 24 weeks after NK-92/5.28.z application with qPCR.
qPCR detection of NK-92/5.28.z in blood or CSF
Measured: 24 weeks
Cytokine profile in the blood and the cerebrospinal fluid.
Measured: 24 weeks
Secondary outcomes (4)
NK-92- and/or CAR 5.28.z-directed immune response.
Measured: 24 weeks
Objective response rate.
Measured: 24 weeks
Progression-free survival.
Measured: 24 weeks
Overall survival.
Measured: 24 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Dec 2017
- Study start1 Dec 2017
- Primary completion31 Dec 2027 (estimated)
- Study completion30 Jun 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for GlioblastomaStudies of the same condition, open and under way.
- 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
- 42 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Johann Wolfgang Goethe University Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- DRK Blutspendedienst Baden-Württemberg-Hessen gGmbH, Georg-Speyer-Haus, LOEWE Center Frankfurt Cancer Institute, German Cancer Research Center
- Responsible party
- Principal investigator, Michael Burger, Johann Wolfgang Goethe University Hospital
- Investigators
- Michael C Burger, PD Dr. med., Principal investigator, Johann W. Goethe University Hospital, Frankfurt am Main, Germany
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03383978
- Sponsor's protocol ID
- EudraCT 2016-000225-39
- Acronym
- CAR2BRAIN
- Status last verified
- Apr 2026
- First submitted
- 30 Nov 2017
- Last updated
- 23 Apr 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 23 Apr 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Multicenter, Open Label, Phase I Study of Intracranial Injection of NK-92/5.28.z Cells in Patients With Recurrent HER2-positive Glioblastoma
- ClinicalTrials.gov ID
- NCT03383978
- Acronym / sponsor ID
- CAR2BRAIN / EudraCT 2016-000225-39
- Conditions
- Glioblastoma
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 42 participants (estimated)
- Lead sponsor
- Johann Wolfgang Goethe University HospitalUniversity, hospital or other
- Collaborators
- DRK Blutspendedienst Baden-Württemberg-Hessen gGmbH, Georg-Speyer-Haus, LOEWE Center Frankfurt Cancer Institute, German Cancer Research Center
- Study start
- 1 Dec 2017 (actual)
- Primary completion
- 31 Dec 2027 (estimated)
- Study completion
- 30 Jun 2028 (estimated)
- First posted
- 27 Dec 2017 (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 main objective of this clinical study is to evaluate the safety and tolerability of NK-92/5.28.z and to determine the maximum tolerated dose or maximum feasible dose (MFD). Recommended phase 2 doses both for intraoperative injections only (RP2Diio) and repetitive injections (RP2Dri) will be determined. Frequent side effects and target organs of toxicity and their severity, duration and reversibility will be determined. Furthermore, pharmacokinetics and pharmacodynamics will be examined. In addition, potential signs of anti-tumor activity of NK-92/5.28.z cells will be analyzed. In the separate "CAR2BRAIN-Check" and "CAR2BRAIN-CheckR" cohorts, combination therapy of NK-92/5.28.z with the anti-PD-1 antibody Ezabenlimab (BI 754091) will be tested.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| NK-92/5.28.z + Ezabenlimab | Experimental | Biological: NK-92/5.28.z, Drug: EzabenlimabIntracranial application of NK-92/5.28.z, 1x10E7-1x10E8; intravenous infusion of Ezabenlimab 240mg q 3 weeks |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (13 listed)
- Recurrent or refractory HER2-positive glioblastoma or its variant gliosarcoma in which relapse surgery (partial or total) or a biopsy (biopsy only for the "CAR2BRAIN-CheckR" cohort) is being planned. Those patients with planned biopsy may be included into the "CAR2BRAIN-CheckR" cohort, if all of the following conditions apply:
- Prior therapy must include the standard of care for glioblastoma (radiotherapy and alkylating chemotherapy, or at least a part thereof if the therapy was terminated prematurely due to therapy failure or poor tolerance). For patients with non-methylated MGMT-Promotor, prior alkylating chemotherapy is dispensable.
- Age ≥ 18 years
- Life expectancy ≥ 3 months
- Bilirubin ≤ 3x normal, AST ≤ 5x normal, ALT ≤ 5x normal, serum creatinine ≤ 2x upper limit of normal for age, leukocyte count ≥ 3/nl, thrombocyte count ≥ 100/nl and Hb ≥ 8.0 g/dl
Key exclusion criteria (19 listed)
- Anti-angiogenic therapy e.g. with bevacizumab in the last four weeks prior to study entry
- Previous anti-PD-1 or anti-PD-L1 directed checkpoint inhibitor therapy (only "CAR2BRAIN-Check" cohort)
- Coagulation disorder (INR>1.4 or PTT>50sec) or anticoagulation in therapeutic dosage
- History of autoimmune disease, including but not limited to myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, vascular thrombosis associated with antiphospholipid syndrome, Wegener's granulomatosis, Sjögren's syndrome, Guillain-Barré syndrome, multiple sclerosis, vasculitis, or glomerulonephritis. However, patients with a history of autoimmune-related hypothyroidism on a stable dose of thyroid replacement hormone may be eligible for this study.
- Patients with Type I diabetes mellitus not on a stable dose of insulin regimen
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 |
|---|---|---|
| NK-92/5.28.zIntracranial application of NK-92/5.28.z, 1x10E7-1x10E8 | Biological | NK-92/5.28.z + Ezabenlimab |
| EzabenlimabIntravenous infusion of Ezabenlimab 240mg q 3 weeks | Drug | NK-92/5.28.z + Ezabenlimab |
Primary outcome
Number of participants with treatment-related adverse events as assessed by CTCAE v4.03.
Time frame: 24 weeks
Maximum tolerated dose (MTD) or maximum feasible dose (MFD) for NK-92/5.28.z
Time frame: 24 weeks
Period of detectability of NK-92/5.28.z cells in blood and cerebrospinal fluid (CSF) during the first 24 weeks after NK-92/5.28.z application with qPCR.
Time frame: 24 weeks
qPCR detection of NK-92/5.28.z in blood or CSF
Cytokine profile in the blood and the cerebrospinal fluid.
Time frame: 24 weeks
4 secondary outcomes
NK-92- and/or CAR 5.28.z-directed immune response.
Time frame: 24 weeks
Objective response rate.
Time frame: 24 weeks
Progression-free survival.
Time frame: 24 weeks
Overall survival.
Time frame: 24 weeks
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 23 Apr 2026.
- Individual participant dataSharing planned: No
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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.
Michael C Burger, PD Dr. med. principal investigator
Johann W. Goethe University Hospital, Frankfurt am Main, Germany
5 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing NK-92/5.28.z and Ezabenlimab in people with Glioblastoma, run by Johann Wolfgang Goethe University Hospital at 5 sites in Germany.
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 13 inclusion and 19 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 23 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 5 sites in Germany. 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 Michael C Burger, PD Dr. med. (0049696301 ext. 87711, michael.burger@unimedizin-ffm.de), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of participants with treatment-related adverse events as assessed by CTCAE v4.03. (time frame: 24 weeks). The study lists 4 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 23 Apr 2026.