CTIM-42. INB-200: PHASE 1 STUDY OF GENE MODIFIED AUTOLOGOUS GAMMA-DELTA (ΓΔ) T CELLS IN NEWLY DIAGNOSED GLIOBLASTOMA MULTIFORME (GBM) PATIENTS RECEIVING MAINTENANCE TEMOZOLOMIDE (TMZ)

Abstract γδ T cells target NKG2D ligands that are upregulated on tumor cells after chemotherapy exposure. IN8bio’s DeltEx drug resistant immunotherapy (DRI) are γδ T cells genetically engineered to express MGMT, conveying TMZ resistance to allow concomitant therapy. We present updated results from this Phase 1 trial, which enrolled adult newly diagnosed glioblastoma patients with adequate organ function, KPS ≥ 70%. Cohorts (C) 1, 2 and 3 received 1, 3 or 6 doses (1 x 107) of DRI cells intratumorally with 150 mg/m2 of TMZ on Day (D) 1 of Stupp maintenance. The primary endpoint is safety and secondary endpoints include survival; immunologic and genomic correlative analyses are included. Dose limiting toxicities (DLTs) are defined as treatment related ≥ grade (G) 3 cardiopulmonary or hepatic toxicity, G4 toxicity exceeding 72 hours or neurologic deterioration that exceeds 2 weeks. 21 patients were enrolled, with 11 dosing (57% male; median age 68 (range: 21-76); 86% IDH-WT, 52% MGMT unmethylated). No DLTs, cytokine release syndrome (CRS) or neurotoxicity (ICANS) reported. Most common adverse events were WBC/platelet count decreased, asthenia, headache, hydrocephalus, decreased appetite and balance disorder. C1 pts had PFS of 8.3, 11.9, 7.4 months (m) and OS of 15.6, 17.7 and 9.6m, respectively. In C2, 1 pt remains progression free at 26.4m, while one progressed at 22m and another died without relapse at 8.7m. C3 pt had a PFS of 7.1 and OS of 13.11m with other pts in dosing. γδ T cells successfully infused with peripheral TMZ-based lymphodepletion evidenced with near or below normal range T, B, and NK subsets for up to 1 year. DRI T cells have manageable toxicity with encouraging trend in PFS with enriched γδ T cell remaining despite peripheral lymphodepletion.