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.
• 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.
• 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%