In:
Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 38, No. 15_suppl ( 2020-05-20), p. 6535-6535
Abstract:
6535 Background: Epstein-Barr virus (EBV) is associated with non-keratinising (NK) NPC, a disease prevalent in Southeast Asia, and provides a potential target for dendritic cell (DC) vaccine therapy. CD137 ligand (CD137L) expressed on antigen presenting cells costimulates CD137 expressing T cells upon receptor/ligand interaction. CD137L signalling differentiates monocytes to CD137L-DC, a novel type of DC, which are more potent than classical DC in stimulating autologous T cells. Here, we explore the safety and efficacy of autologous CD137L-DC pulsed with EBV peptides spanning Epstein Barr nuclear antigen 1, latent membrane protein 1 (LMP1) and LMP2 (CD137L-DC-EBV-VAX) in patients with locally recurrent or metastatic NPC. Methods: In this single centre, phase I study, eligible patients (pts) with locally recurrent or metastatic NK-NPC and clinical benefit (CB) from their prior treatment (stable disease [SD], partial [PR] or complete response[CR]), underwent apheresis to isolate monocytes which were differentiated to CD137L-DC through CD137L agonist exposure. CD137L-DC were pulsed with EBV antigens during maturation to obtain CD137L-DC-EBV-VAX which was administered intradermally every 2 weeks (w) for up to 7 injections following site preconditioning with Tetanus and Diphtheria vaccine. Results: 14 pts were enrolled of which 2 progressed rapidly and did not begin treatment. Mean age was 58 years. Median lines of prior treatment for metastatic NPC was 1 (range 1-6), the most common being cisplatin and gemcitabine. 9 pts received 7 vaccine doses (range 2-7) with a mean administered cell count of 23.9x10 6 . CB was seen in 5 cases (42%) with 1 PR and 4 SD beyond 1 year. Median progression free survival (mPFS) was 26w (95% CI, 23-43). The lowest PFS (8w) was in a pt with 6 prior lines of treatment including a checkpoint inhibitor. Mean pretreatment neutrophil: lymphocyte ratio (NLR) was 3.4 and a value of less than 3 was associated with prolonged mPFS (42 vs 14w, p = 0.01). Enzyme linked immune absorbent spot (ELISPOT) analysis in 5 pts with CB showed a rise in interferon-γ secreting peripheral T cells prior to the 3 rd vaccine versus baseline. Treatment was well tolerated with only 4 cases of grade 1 related adverse events reported, most commonly injection site reaction (3pts). Conclusions: CD137L-DC-EBV-VAX is safe and exhibits promising efficacy when administered following CB from chemotherapy. A rise in activated peripheral blood mononuclear cells after 2 vaccinations in selected patients showing benefit suggests immunological correlates with efficacy. Clinical trial information: NCT03282617 .
Type of Medium:
Online Resource
ISSN:
0732-183X
,
1527-7755
DOI:
10.1200/JCO.2020.38.15_suppl.6535
Language:
English
Publisher:
American Society of Clinical Oncology (ASCO)
Publication Date:
2020
detail.hit.zdb_id:
2005181-5
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