EBV Lytic Reactivation Therapy Combined With PD-1 Antibody in Recurrent/Metastatic Nasopharyngeal Carcinoma

Summary

Nearly all undifferentiated nasopharyngeal carcinoma (NPC) are associated with the Epstein-Barr Virus (EBV), which typically remains in a latent, non-immunogenic state within tumor cells. By combining EBV lytic induction strategy with standard chemo-immunotherapy, this study aims to create a synergistic anti-tumor effect and improve clinical outcomes for patients with recurrent/metastatic NPC (r/m NPC). This is a phase II, single-center, single-arm clinical trial designed to evaluate the efficacy and safety of a novel combination therapy in patients with r/m EBV-positive NPC.

Timeline

Start

2025-08-19

Primary completion

2026-08-18

Completion

2031-08-18

Publications

• Background Ghosh SK, Perrine SP, Williams RM, Faller DV. Histone deacetylase inhibitors are potent inducers of gene expression in latent EBV and sensitize lymphoma cells to nucleoside antiviral agents. Blood. 2012 Jan 26;119(4):1008-17. doi: 10.1182/blood-2011-06-362434. Epub 2011 Dec 7.
• Background Perrine SP, Hermine O, Small T, Suarez F, O'Reilly R, Boulad F, Fingeroth J, Askin M, Levy A, Mentzer SJ, Di Nicola M, Gianni AM, Klein C, Horwitz S, Faller DV. A phase 1/2 trial of arginine butyrate and ganciclovir in patients with Epstein-Barr virus-associated lymphoid malignancies. Blood. 2007 Mar 15;109(6):2571-8. doi: 10.1182/blood-2006-01-024703. Epub 2006 Nov 21.
• Background Wu M, Hau PM, Li L, Tsang CM, Yang Y, Taghbalout A, Chung GT, Hui SY, Tang WC, Jillette N, Zhu JJ, Lee HHY, Kong EL, Chan MSA, Chan JYK, Ma BBY, Chen MR, Lee C, To KF, Cheng AW, Lo KW. Synthetic BZLF1-targeted transcriptional activator for efficient lytic induction therapy against EBV-associated epithelial cancers. Nat Commun. 2024 May 3;15(1):3729. doi: 10.1038/s41467-024-48031-8.
• Background Mai HQ, Chen QY, Chen D, Hu C, Yang K, Wen J, Li J, Shi Y, Jin F, Xu R, Pan J, Qu S, Li P, Hu C, Liu YC, Jiang Y, He X, Wang HM, Lim WT, Liao W, He X, Chen X, Wang S, Yuan X, Li Q, Lin X, Jing S, Chen Y, Lu Y, Hsieh CY, Yang MH, Yen CJ, Samol J, Luo X, Wang X, Tang X, Feng H, Yao S, Keegan P, Xu RH. Toripalimab Plus Chemotherapy for Recurrent or Metastatic Nasopharyngeal Carcinoma: The JUPITER-02 Randomized Clinical Trial. JAMA. 2023 Nov 28;330(20):1961-1970. doi: 10.1001/jama.2023.20181.

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Indications