A Phase III Trial Evaluating Chemotherapy and Immunotherapy for Advanced Nasopharyngeal Carcinoma (NPC) Patients

Summary

This study is a multi-center, randomized, open label, Phase III clinical trial for advanced Nasopharyngeal Carcinoma(NPC) Patients. Drugs used in chemotherapy, such as gemcitabine and carboplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving an infusion of a person's cytotoxic T cells (CTL) that have been treated in the laboratory may help the body build an effective immune response to kill tumor cells. Giving combination chemotherapy together with laboratory-treated T cells may kill more tumor cells. This Phase III trial is to assess if combined gemcitabine-carboplatin (GC) followed by adoptive T-cell therapy would improve clinical outcome for patients with advanced nasopharyngeal carcinoma (NPC). It is also the world's first, and largest, Phase 3 T-cell therapy cancer trial ever conducted, and enrollment is ongoing for 330 patients from 30 hospital centers across Asia and the United States. This clinical trial is conducted on the back of a successful Phase 2 NPC trial involving 38 patients at the National Cancer Centre, Singapore. This trial produced the best published 2-year (62.9%), and median overall survival (OS) data (29.9 months) in 35 patients with advanced NPC who received autologous EBV-specific CTL. Kindly see https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3978790/ for the Phase 2 publication titled "Adoptive T-cell Transfer and Chemotherapy in the First line treatment of Metastatic and/or Locally Recurrent Nasopharyngeal Carcinoma".

Timeline

Start

2014-07

Primary completion

2022-02-28

Completion

2022-02-28

Outcome

Missed primary endpoint

registry analysis (superiority test); Chemo + EBV-CTL vs Chemo Only; p = 0.1942; Hazard Ratio (HR) 1.19 (95% CI 0.91 to 1.56) NCT02578641 ↗

paper GC + EBV-CTL in subjects with R/M NPC demonstrated a favorable safety profile but no overall improvement in OS versus chemotherapy. PMID 39241963 ↗

Publications

• Toh HC, Yang MH, Wang HM, Hsieh CY, Chitapanarux I, Ho KF, Hong RL, Ang MK, Colevas AD, Sirachainan E, Lertbutsayanukul C, Ho GF, Nadler E, Algazi A, Lulla P, Wirth LJ, Wirasorn K, Liu YC, Ang SF, Low SHJ, Tho LM, Hasbullah HH, Brenner MK, Wang WW, Ong WS, Tan SH, Horak I, Ding C, Myo A, 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. Ann Oncol. 2024 Dec;35(12):1181-1190. doi: 10.1016/j.annonc.2024.08.2344. Epub 2024 Sep 4.

Drugs

Evaluation	Drug	Modality	Dose	Route
Subject	Carboplatin	Small molecule	2 unknown	Intravenous
Subject	Gemcitabine	Small molecule	1000 mg/m2	Intravenous
Subject	tabelecleucel	Cell therapy	—	—

Indications