Key points are not available for this paper at this time.
2042 Background: γδ T cells can target NKG2D ligands that are upregulated on tumor cells after alkylating chemotherapy exposure. IN8bio’s DeltEx drug resistant immunotherapy (DRI) are genetically engineered γδ T cells expressing methylguanine-DNA methyltransferase (MGMT), which conveys TMZ resistance to enable concomitant therapy and continued surveillance against tumor cells. Updated results from the Phase 1 trial which fully enrolled adult newly diagnosed GBM patients with adequate organ function, KPS ≥ 70% follow. Methods: Cohorts (C) 1, 2 and 3 received 1, 3 or 6 doses (1 x 10 7 DRI cells/dose) into the resection cavity with 150 mg/m 2 of IV TMZ on Day (D) 1 of each Stupp maintenance cycle. 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. Results: 23 patients were enrolled, with 11 dosed and 2 awaiting dosing (61% male; median age 68 (range: 21-74); 92% IDH-WT, 54% MGMT unmethylated). No DLTs, cytokine release syndrome (CRS) or neurotoxicity (ICANS) are reported. Most common adverse events were decreased WBC/platelet count, asthenia, fatigue, hydrocephalus, headache, decreased appetite, urinary tract infection, thrombosis and balance disorder. Conclusions: 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. The majority of dosed patients who received DRI exceeded the expected median PFS of 7 months (5.8-8.2 months) with Stupp alone and had manageable toxicity with a continued encouraging trend in PFS. Long-term follow-up for durability of PFS and OS continue. Clinical trial information: NCT04165941 . Table: see text
Lobbous et al. (Sat,) studied this question.