Intracranial Injection of NK-92/5.28.z Cells in Combination With Intravenous Ezabenlimab in Patients With Recurrent HER2-positive Glioblastoma

NCT03383978 | Recruiting Phase 1

• 1 other identifier: EudraCT 2016-000225-39
• Study Type: interventional
• Target: 42
• Locations: 1 country
• Sites: 5

Brief 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. 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

Outcome Measures

Primary Outcomes (4)

• Number of participants with treatment-related adverse events as assessed by CTCAE v4.03.

  24 weeks

• Maximum tolerated dose (MTD) or maximum feasible dose (MFD) for NK-92/5.28.z

  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

  24 weeks

• Cytokine profile in the blood and the cerebrospinal fluid.

  24 weeks

Secondary Outcomes (4)

• NK-92- and/or CAR 5.28.z-directed immune response.

  24 weeks

• Objective response rate.

  24 weeks

• Progression-free survival.

  24 weeks

• Overall survival.

  24 weeks

Study Arms (1)

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

Biological: NK-92/5.28.z; Drug: Ezabenlimab

Interventions

NK-92/5.28.z BIOLOGICAL

Intracranial application of NK-92/5.28.z, 1x10E7-1x10E8

NK-92/5.28.z + Ezabenlimab

Ezabenlimab DRUG

Intravenous infusion of Ezabenlimab 240mg q 3 weeks

NK-92/5.28.z + Ezabenlimab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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.
• Informed consent explained to and signed by patient; patient given copy of informed consent.
• Karnofsky performance score of ≥ 70%

You may not qualify if:

• 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:
• 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

Sponsors & Collaborators

• Johann Wolfgang Goethe University Hospital: lead
• DRK Blutspendedienst Baden-Württemberg-Hessen gGmbH: collaborator
• Georg-Speyer-Haus: collaborator
• LOEWE Center Frankfurt Cancer Institute: collaborator
• German Cancer Research Center: collaborator

Study Sites (5)

Neurochirurgische Klinik, Universitätsklinikum Heidelberg

Heidelberg, Baden-Wurttemberg, 69120, Germany

RECRUITING

Neurochirurgische Klinik, Universitätsmedizin Mannheim

Mannheim, Baden-Wurttemberg, 68167, Germany

RECRUITING

Neurochirurgische Klinik, Universitätsmedizin Mainz

Mainz, Rhineland-Palatinate, 55131, Germany

RECRUITING

Johann W. Goethe University Hospital, Department of Neurosurgery

Frankfurt, 60590, Germany

RECRUITING

Johann W. Goethe University Hospital, Senckenberg Institute of Neurooncology

Frankfurt, 60590, Germany

RECRUITING

Related Links

• Sponsor homepage

MeSH Terms

Conditions

Glioblastoma

Condition Hierarchy (Ancestors)

Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Study Officials

• Michael C Burger, PD Dr. med.

  Johann W. Goethe University Hospital, Frankfurt am Main, Germany

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Michael C Burger, PD Dr. med.

CONTACT

0049696301; michael.burger@unimedizin-ffm.de

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: November 30, 2017
• First Posted: December 27, 2017
• Study Start: December 1, 2017
• Primary Completion (Estimated): December 31, 2027
• Study Completion (Estimated): June 30, 2028
• Last Updated: April 23, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

DE (5)