Phase I study of repeated peripheral infusions of anti-EGFRvIII CAR T cells in combination with pembrolizumab in patients with newly diagnosed, MGMT-unmethylated glioblastoma
Research Square (Research Square)(2023)
Abstract
Abstract Treatment efficacy with chimeric antigen receptor (CAR) T cell therapy in glioblastoma (GBM) is undermined by an immunosuppressive tumor microenvironment (TME). We previously showed that CAR T cell therapy targeting epidermal growth factor receptor variant III (EGFRvIII) produces anti-tumor activity against recurrent GBM and causes upregulation of programmed death-ligand 1 (PD-L1) in the TME. Here, we conducted a phase I trial to study the impact of CART-EGFRvIII cells administered concomitantly with the PD-1 inhibitor pembrolizumab in patients (n = 7) with newly diagnosed, EGFRvIII + GBM. Treatment was well tolerated without incidence of dose-limiting toxicity. However, no signal of efficacy was detected with a median progression-free survival of 5.2 months (90% CI, 2.9–6.0 months) and median overall survival of 11.8 months (90% CI, 9.2–14.2 months). In addition, PD-1 expression in the CART-EGFRvIII infusion product did not correlate with outcomes, and peripheral CAR T cell engraftment was relatively short-lived. Together, these findings show the safety of combining CAR T cells and PD-1 inhibition in GBM but given the lack of efficacy, also indicate a need to consider alternative combinatorial strategies. ClinicalTrials.gov registration: NCT03726515.
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Key words
pembrolizumab,anti-egfrviii,mgmt-unmethylated
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