Gemcitabine, carboplatin, and Epstein-Barr virus-specific autologous cytotoxic T lymphocytes for recurrent or metastatic nasopharyngeal carcinoma: VANCE, an international randomized phase III trial

Authors

• H. C. Toh
• M. -h. Yang
• H. -m. Wang
• C. Y. Hsieh
• I. Chitapanarux
• K. F. Ho
• R. -l. Hong
• M. K. Ang
• A. D. Colevas
• E. Sirachainan
• C. Lertbutsayanukul
• G. F. Ho
• E. Nadler
• A. Algazi
• P. Lulla
• L. J. Wirth
• K. Wirasorn
• Y. C. Liu
• S. F. Ang
• S. H. J. Low
• L. M. Tho
• H. H. Hasbullah
• M. K. Brenner
• W. -w. Wang
• W. S. Ong
• S. H. Tan
• I. Horak
• C. Ding
• A. Myo
• J. Samol

Document Type

Article

Publication Date

12-1-2024

Abstract

Background: Epstein-Barr virus-specific cytotoxic T lymphocyte (EBV-CTL) is an autologous adoptive T-cell immunotherapy generated from the blood of individuals and manufactured without genetic modification. In a previous phase II trial of locally recurrent or metastatic nasopharyngeal carcinoma (R/M NPC) patients, fi rst-line gemcitabine and carboplatin (GC) and EBV-CTL combination demonstrated objective antitumor EBV-CTL activity and a favorable safety profile. The present study explored whether this combined fi rst-line chemo-immunotherapy strategy would produce superior clinical efficacy and better quality of life compared with conventional chemotherapy treatment. Patients and methods: This multicenter, randomized, phase III trial evaluated the efficacy and safety of GC followed by EBVCTL versus GC alone as fi rst-line treatment of R/M NPC patients. Thirty clinical sites in Singapore, Malaysia, Taiwan, Thailand, and the USA were included. Subjects were randomized to fi rst-line GC (four cycles) and EBV-CTL (six cycles) or GC (six cycles) in a 1 : 1 ratio. The primary outcome was overall survival (OS) and secondary outcomes included progression-free survival, objective response rate, clinical benefit rate, quality of life, and safety. ClinicalTrials.gov identifier: NCT02578641. Results: A total of 330 subjects with NPC were enrolled. Most subjects in both treatment arms received four or more cycles of chemotherapy and most subjects in the GC + EBV-CTL group received two or more infusions of EBV-CTL. The central Good Manufacturing Practices (GMP) facility produced sufficient EBV-CTL for 94% of GC + EBV-CTL subjects. The median OS was 25.0 months in the GC + EBV-CTL group and 24.9 months in the GC group (hazard ratio = 1.19; 95% confidence interval 0.911.56; P = 0.194). Only one subject experienced a grade 2 serious adverse event related to EBV-CTL. Conclusions: GC+ EBV-CTL in subjects with R/M NPC demonstrated a favorable safety profile but no overall improvement in OS versus chemotherapy. This is the largest adoptive T-cell therapy trial reported in solid tumors to date.

Keywords

Epstein-Barr virus cytotoxic T lymphocytes, nasopharyngeal carcinoma, adoptive T-cell therapy, cancer immunotherapy, randomized phase III trial

Publication Title

Annals of Oncology

Recommended Citation

Toh, H. C.; Yang, M. -h.; Wang, H. -m.; Hsieh, C. Y.; Chitapanarux, I.; Ho, K. F.; Hong, R. -l.; Ang, M. K.; Colevas, A. D.; Sirachainan, E.; Lertbutsayanukul, C.; Ho, G. F.; Nadler, E.; Algazi, A.; Lulla, P.; Wirth, L. J.; Wirasorn, K.; Liu, Y. C.; Ang, S. F.; Low, S. H. J.; Tho, L. M.; Hasbullah, H. H.; Brenner, M. K.; Wang, W. -w.; Ong, W. S.; Tan, S. H.; Horak, I.; Ding, C.; Myo, A.; and Samol, J., "Gemcitabine, carboplatin, and Epstein-Barr virus-specific autologous cytotoxic T lymphocytes for recurrent or metastatic nasopharyngeal carcinoma: VANCE, an international randomized phase III trial" (2024). Research Publications (2021 to 2025). 6096.
https://knova.um.edu.my/research_publications_2021_2025/6096

Divisions

fac_med

Volume

35

Issue

12

Publisher

Elsevier

Publisher Location

RADARWEG 29, 1043 NX AMSTERDAM, NETHERLANDS