Fulltext

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

Toh HC 1 , Yang MH 2 , Wang HM 3 , Hsieh CY 4 , Chitapanarux I 5 , Ho KF 6 Show all authors , Hong RL 7 , Ang MK 8 , Colevas AD 9 , Sirachainan E 10 , Lertbutsayanukul C 11 , Ho GF 12 , Nadler E 13 , Algazi A 14 , Lulla P 15 , Wirth LJ 16 , Wirasorn K 17 , Liu YC 18 , Ang SF 19 , Low SHJ 20 , Tho LM 21 , Hasbullah HH 22 , Brenner MK 15 , Wang WW 8 , Ong WS 23 , Tan SH 23 , Horak I 24 , Ding C 24 , Myo A 24 , Samol J 25

Affiliations 

  • 1 Division of Medical Oncology, National Cancer Centre Singapore, Singapore. Electronic address: toh.han.chong@singhealth.com.sg
  • 2 Department of Oncology, Taipei Veterans General Hospital, Taipei
  • 3 Division of Hematology/Oncology, Department of Internal Medicine, Chang Gung Memorial Hospital-Linkou, Taoyuan City
  • 4 Division of Hematology and Oncology, Department of Internal Medicine, China Medical University Hospital, Taichung City, Taiwan
  • 5 Department of Radiology, Chiang Mai University, Chiang Mai, Thailand
  • 6 Clinical Oncology Unit, Mount Miriam Cancer Hospital, Tanjung Bungah, Malaysia
  • 7 Department of Oncology, National Taiwan University Hospital, Taipei, Taiwan
  • 8 Division of Medical Oncology, National Cancer Centre Singapore, Singapore
  • 9 Division of Medical Oncology, Stanford University School of Medicine, Stanford, USA
  • 10 Department of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok
  • 11 Department of Radiology, King Chulalongkorn Memorial Hospital, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand
  • 12 Department of Clinical Oncology, University of Malaya, Kuala Lumpur, Malaysia
  • 13 Texas Oncology-Baylor Charles A. Sammons Cancer Centre, Dallas
  • 14 Division of Hematology and Oncology, University of California, San Francisco
  • 15 Center for Cell and Gene Therapy, Baylor College of Medicine, Houston Methodist Hospital and Texas Children's Hospital, Houston
  • 16 Harvard Medical School, Massachusetts General Hospital, Boston, USA
  • 17 Department of Medicine, Srinagarind Khon Kaen University Hospital, Khon Kaen, Thailand
  • 18 Department of Radiation-Oncology, Veterans General Hospital-Taichung, Taichung, Taiwan
  • 19 Penang Adventist Hospital, Penang
  • 20 Pantai Hospital Kuala Lumpur, Kuala Lumpur
  • 21 Beacon Hospital, Selangor
  • 22 Hospital Kuala Lumpur, Kuala Lumpur, Malaysia
  • 23 Division of Clinical Trials and Epidemiological Sciences, National Cancer Centre Singapore, Singapore
  • 24 Tessa Therapeutics Ltd, Singapore
  • 25 Department of Medical Oncology, Clinical Trials, CRIO, P.H. Feng Research Centre, Tan Tock Seng Hospital, Singapore; Lee Kong Chian School of Medicine, Singapore; Johns Hopkins University, Baltimore, USA
Ann Oncol, 2024 Dec;35(12):1181-1190.
PMID: 39241963 DOI: 10.1016/j.annonc.2024.08.2344

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, 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.

PATIENTS AND METHODS: 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.

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 0.91-1.56; 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.

* Title and MeSH Headings from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

MeSH terms
Similar publications