학술논문
Repeated peripheral infusions of anti-EGFRvIII CAR T cells in combination with pembrolizumab show no efficacy in glioblastoma: a phase 1 trial
Document Type
Original Paper
Author
Bagley, Stephen J.; Binder, Zev A.; Lamrani, Lamia; Marinari, Eliana; Desai, Arati S.; Nasrallah, MacLean P.; Maloney, Eileen; Brem, Steven; Lustig, Robert A.; Kurtz, Goldie; Alonso-Basanta, Michelle; Bonté, Pierre-Emmanuel; Goudot, Christel; Richer, Wilfrid; Piaggio, Eliane; Kothari, Shawn; Guyonnet, Lea; Guerin, Coralie L.; Waterfall, Joshua J.; Mohan, Suyash; Hwang, Wei-Ting; Tang, Oliver Y.; Logun, Meghan; Bhattacharyya, Meghna; Markowitz, Kelly; Delman, Devora; Marshall, Amy; Wherry, E. John; Amigorena, Sebastian; Beatty, Gregory L.; Brogdon, Jennifer L.; Hexner, Elizabeth; Migliorini, Denis; Alanio, Cecile; O’Rourke, Donald M.
Source
Nature Cancer. 5(3):517-531
Subject
Language
English
ISSN
2662-1347
Abstract
We previously showed that chimeric antigen receptor (CAR) T-cell therapy targeting epidermal growth factor receptor variant III (EGFRvIII) produces upregulation of programmed death-ligand 1 (PD-L1) in the tumor microenvironment (TME). Here we conducted a phase 1 trial (NCT03726515) of CAR T-EGFRvIII cells administered concomitantly with the anti-PD1 (aPD1) monoclonal antibody pembrolizumab in patients with newly diagnosed, EGFRvIII+ glioblastoma (GBM) (n = 7). The primary outcome was safety, and no dose-limiting toxicity was observed. Secondary outcomes included median progression-free survival (5.2 months; 90% confidence interval (CI), 2.9–6.0 months) and median overall survival (11.8 months; 90% CI, 9.2–14.2 months). In exploratory analyses, comparison of the TME in tumors harvested before versus after CAR + aPD1 administration demonstrated substantial evolution of the infiltrating myeloid and T cells, with more exhausted, regulatory, and interferon (IFN)-stimulated T cells at relapse. Our study suggests that the combination of CAR T cells and PD-1 inhibition in GBM is safe and biologically active but, given the lack of efficacy, also indicates a need to consider alternative strategies.
Bagley et al. conduct a phase 1 trial to study safety and tolerability of CAR T-EGFRvIII cells administered concomitantly with PD-1 inhibition via pembrolizumab in patients with glioblastoma and show tolerability, but without signs of efficacy.
Bagley et al. conduct a phase 1 trial to study safety and tolerability of CAR T-EGFRvIII cells administered concomitantly with PD-1 inhibition via pembrolizumab in patients with glioblastoma and show tolerability, but without signs of efficacy.