Background: MHC unrestricted γδ T cells target NKG2D ligands upregulated on tumor cells. IN8bio’s DeltEx chemotherapy resistant cell therapy (CRCT), is a novel γδ T cell genetically engineered to express MGMT to convey temozolomide (TMZ) resistance and allow combination therapy. NCT04165941, a Phase 1 trial assessing the safety of single and multiple infusions of autologous CRCT cells presents updated safety and efficacy data. Methods: Adult newly diagnosed GBM patients with adequate organ function and KPS≥70% are enrolled. Cells engineered from apheresis were infused through a Rickham catheter placed during surgery. Cohorts (C) 1, 2 and 3 each receive 1, 3 and6 doses of cells respectively on day (D) 1 of each 28-day maintenance cycle. Patients receive 1 x 10⁷γδ T cells intratumorally with 150 mg/m² of TMZ intravenously on D1 of maintenance with the standard Stupp maintenance regimen on D2-5. Primary endpoint is safety; secondary endpoints include progression free and overall survival. Immunologic and genomic correlative analyses are being conducted. Dose limiting toxicities (DLTs) are defined as treatment related ≥ grade 3 cardiopulmonary or hepatic toxicity, grade 4 toxicity exceeding 72 hours or neurologic deterioration that exceeds 2 weeks. Results: 15 patients (53% male; median age 69 (range: 21-76); 80% IDH-WT, 66.7% MGMT unmethylated) were enrolled with 8 dosed (N=3 in C1, 4 in C2, 1 in C3). No patients experienced DLTs, cytokine release syndrome (CRS), or neurotoxicity (ICANS). The most common adverse events (AEs) were Grade 1/2 events including fever, fatigue, nausea, headache, platelet count decreased, incision site pain attributable to TMZ, radiotherapy or disease. One subject had Grade 3 treatment related AEs of UTI, dehydration, and thrombocytopenia. Three evaluable C1 patients have PFS of 8.3, 11.9, 7.4 months and OS of 15.6, 17.7 and 9.6 months respectively. In C2, four patients have been dosed, with no DLTs in 3 evaluable patients; 2 remain progression free at 18.9 and 14.8 months, while a third died without relapse due to pulmonary embolus at 8.7 months. One C3 patient has completed 5 of 6 planned doses without DLT. Patient recruitment continues with anticipated completion in 2023. Conclusions: Data demonstrates that single, repeat doses of CRCT gamma delta T cells have manageable toxicity with continued encouraging trend in PFS and warrants further assessment. Clinical trial information: NCT04165941.