CTIM-17. INB-200: PHASE 1 STUDY AND CHARACTERIZATION OF GENE-MODIFIED AUTOLOGOUS GAMMA-DELTA (ΓΔ) T CELLS IN GLIOBLASTOMA MULTIFORME (GBM) PATIENTS RECEIVING MAINTENANCE TEMOZOLOMIDE (TMZ)

Abstract Cell therapy for GBM holds significant promise but previous studies have not demonstrated meaningful therapeutic durability or improved progression free survival. This fully enrolled Phase 1 trial of INB-200 in newly diagnosed GBM uses drug resistant immunotherapy (DRI), MGMT-gene modified γδ T cells engineered for TMZ resistance. These cells are concurrently dosed to leverage TMZ-induced transient upregulation of NKG2DL on GBM cells, to identify and eradicate any residual cancer cells. A total of 23 patients were enrolled, with 13 treated (median age 66 (range: 21-75); 92% IDH-WT, 54% MGMT-unmethylated, 46% subtotal resection). Cohorts 1, 2 and 3 received 1, 3 or 6 doses (1x107 DRI cells/dose) into the resection cavity with 150 mg/m2 of IV TMZ on Day 1 of each Stupp maintenance cycle. No DLTs, cytokine release syndrome (CRS), neurotoxicity (ICANS) or treatment related deaths were reported. The median PFS for all repeat dose patients is 16.1 months, +132.6% over Stupp (6.9m) and +94.2% over single dose patients (8.3m). The mPFS of multidose patients exceeds the expected OS Stupp SOC of 14.6m. One patient with a grade-4, IDH mutant tumor remains progression free for >48 months. Additionally, durability of the product was demonstrated in biopsy specimens from two patients with small recurrent tumors that showed significant ongoing γδT cell infiltration and tumor necrosis well beyond the final dose of DRI γδT cells. To contextualize the clinical results, we analyzed paired starting material and final manufactured cell products from a subset of autologous INB-200 DeltEx DRI using TCR repertoire and gene expression profiling. This revealed upregulation of cytotoxicity-associated genes (e.g., IFNG, GZMB, PRF1), markers of activation and immune cell trafficking. Expression patterns were consistent, underscoring manufacturing robustness and reproducibility. These Phase I findings demonstrate safety, manufacturing consistency, and encouraging durability of both the infused cells and clinical response.