Gemcitabine, carboplatin, and Epstein-Barr virus-specific autologous cytotoxic T lymphocytes for recurrent or metastatic nasopharyngeal carcinoma: VANCE, an international randomized phase III trial.
Journal
Annals of oncology : official journal of the European Society for Medical Oncology
ISSN
0923-7534
Date Issued
2024-09-04
Author(s)
Toh, H C
Yang, M-H
Wang, H-M
Hsieh, C Y
Chitapanarux, I
Ho, K F
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
Samol, J
Abstract
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, first-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 first-line chemo-immunotherapy strategy would produce superior clinical efficacy and better quality of life compared with conventional chemotherapy treatment.
This multicenter, randomized, phase III trial evaluated the efficacy and safety of GC followed by EBV-CTL versus GC alone as first-line treatment of R/M NPC patients. Thirty clinical sites in Singapore, Malaysia, Taiwan, Thailand, and the USA were included. Subjects were randomized to first-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.
gov identifier: NCT02578641.
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 0.91-1.56; P = 0.194). Only one subject experienced a grade 2 serious adverse event related to EBV-CTL.
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.
Subjects
Epstein–Barr virus cytotoxic T lymphocytes
adoptive T-cell therapy
cancer immunotherapy
nasopharyngeal carcinoma
randomized phase III trial
Type
journal article