Phase 1 Study of Locally Delivered Dual-Target CAR-NK Cells for Adults With Recurrent or Progressive Glioblastoma and High-Grade Glioma

What this Trial Is About

Researchers are evaluating a first-in-human phase 1 study to assess a new treatment using dual-targeting chimeric antigen receptor natural killer CAR-NK cells for adults with recurrent or progressive glioblastoma GBM or other high-grade gliomas HGG. The study aims to reduce tumor escape by targeting two tumor-associated antigens selected from IL13R2, EGFREGFRvIII, and B7-H3 CD276. Participants undergo tumor antigen profiling to determine the most suitable dual-target CAR construct based on their tumors antigen expression. The investigational CAR-NK cells are off-the-shelf allogeneic natural killer cells genetically modified to express a tandem dual-target CAR. They are delivered directly to the tumor site via a catheter or reservoir placed during neurosurgery, targeting the surgical cavity wall or ventricular system to maximize local exposure while minimizing systemic effects. Dose escalation follows a modified 33 schema with up to three dose levels, followed by an expansion phase to further evaluate safety and possible repeated infusions at the recommended dose. Lymphodepleting chemotherapy with cyclophosphamide and fludarabine is given prior to CAR-NK infusion. Participants will have tumor response monitored by MRI using RANO criteria and be closely followed for adverse events including cytokine release syndrome and neurotoxicity. Tumor antigen testing involves immunohistochemistry and molecular methods using fresh or archived tumor tissue. Long-term safety follow-up will continue according to gene-modified cell therapy guidelines. The study includes assessments of dose-limiting toxicities during the first 28 days and determination of recommended phase 2 dose over 12 months. Total participation may last up to or beyond one year with regular safety and response evaluations.

Dual-Targeting CAR-NK Cells for Recurrent/Progressive Glioblastoma and High-Grade Glioma