CTIM-09. INB-200: FULLY ENROLLED PHASE 1 STUDY OF GENE-MODIFIED AUTOLOGOUS GAMMA-DELTA (ΓΔ) T CELLS IN NEWLY DIAGNOSED GLIOBLASTOMA MULTIFORME (GBM) PATIENTS RECEIVING MAINTENANCE TEMOZOLOMIDE (TMZ)

Abstract IN8bio’s DeltEx drug resistant immunotherapy (DRI), comprising TMZ-resistant γδ T cells engineered to express methylguanine-DNA methyltransferase (MGMT), enables γδ T cells to target upregulated NKG2D ligands on tumor cells in real time during alkylating chemotherapy exposure. Updated results from the fully enrolled Phase 1 trial evaluating DRI in adult newly diagnosed GBM subjects with IDH wild type and mutant tumors, adequate organ function and KPS ≥ 70%. Cohorts (C) 1, 2 and 3 received 1, 3 or 6 doses (1 x 107 DRI cells/dose) into the resection cavity with 150 mg/m2 of IV TMZ on Day 1 of each of 6 Stupp maintenance cycles. The primary endpoint is safety and secondary endpoints include survival; immunologic 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. A total of 23 subjects were enrolled and 13 dosed (61% male; median age 68 (range: 21-74); 92% IDH-WT, 54% MGMT unmethylated). No DLTs, cytokine release syndrome (CRS), neurotoxicity (ICANS) or treatment related deaths were reported. The most common adverse events were decreased WBC/platelet count, asthenia, fatigue, hydrocephalus, headache, decreased appetite, urinary tract infection, thrombosis and balance disorder with ≥G3 platelet count decreased in 23% and WBC/ neutrophil/ lymphocyte count decreased in 7.7% each. Peripheral TMZ-based lymphodepletion was maintained for up to 1 year evidenced by near or below normal range T, B, and NK subsets. With median follow-up of 10.8 months, 83% of subjects exceeded the median 7 month Progression Free Survival (PFS) of the Stupp regimen alone, had manageable toxicity with a continued encouraging trend in PFS. Subject with IDH mutant tumor remains progression free for > 35 months. Long-term follow-up for durability of PFS and OS continues.