Results of a randomized, double-blind phase II clinical trial of NY-ESO-1 vaccine with ISCOMATRIX adjuvant versus ISCOMATRIX alone in participants with high-risk resected melanoma

Cebon, J. S. et al. (2020) Results of a randomized, double-blind phase II clinical trial of NY-ESO-1 vaccine with ISCOMATRIX adjuvant versus ISCOMATRIX alone in participants with high-risk resected melanoma. Journal for ImmunoTherapy of Cancer, 8(1), e000410. (doi: 10.1136/jitc-2019-000410) (PMID:32317292) (PMCID:PMC7204806)

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Background: To compare the clinical efficacy of New York Esophageal squamous cell carcinoma-1 (NY-ESO-1) vaccine with ISCOMATRIX adjuvant versus ISCOMATRIX alone in a randomized, double-blind phase II study in participants with fully resected melanoma at high risk of recurrence. Methods: Participants with resected stage IIc, IIIb, IIIc and IV melanoma expressing NY-ESO-1 were randomized to treatment with three doses of NY-ESO-1/ISCOMATRIX or ISCOMATRIX adjuvant administered intramuscularly at 4-week intervals, followed by a further dose at 6 months. Primary endpoint was the proportion free of relapse at 18 months in the intention-to-treat (ITT) population and two per-protocol populations. Secondary endpoints included relapse-free survival (RFS) and overall survival (OS), safety and NY-ESO-1 immunity. Results: The ITT population comprised 110 participants, with 56 randomized to NY-ESO-1/ISCOMATRIX and 54 to ISCOMATRIX alone. No significant toxicities were observed. There were no differences between the study arms in relapses at 18 months or for median time to relapse; 139 vs 176 days (p=0.296), or relapse rate, 27 (48.2%) vs 26 (48.1%) (HR 0.913; 95% CI 0.402 to 2.231), respectively. RFS and OS were similar between the study arms. Vaccine recipients developed strong positive antibody responses to NY-ESO-1 (p≤0.0001) and NY-ESO-1-specific CD4+ and CD8+ responses. Biopsies following relapse did not demonstrate differences in NY-ESO-1 expression between the study populations although an exploratory study demonstrated reduced (NY-ESO-1)+/Human Leukocyte Antigen (HLA) class I+ double-positive cells in biopsies from vaccine recipients performed on relapse in 19 participants. Conclusions: The vaccine was well tolerated, however, despite inducing antigen-specific immunity, it did not affect survival endpoints. Immune escape through the downregulation of NY-ESO-1 and/or HLA class I molecules on tumor may have contributed to relapse.

Item Type:Articles
Additional Information:This clinical study was sponsored and funded by the Ludwig Institute for Cancer Research. Certain proprietary rights to NY-ESO-1 have been licensed by the Ludwig Institute to CSL, which participated in the clinical study through the provision of clinical reagents and additional logistical support. JSC acknowledges support from the Cancer Research Institute, USA. AB acknowledges support from the Ian Potter Foundation, grant No. 20150678, and Operational Infrastructure Support Program Funding of the Victorian State Government. VC acknowledges support from the UK Medical Research Council and from Cancer Research UK (Programme grant #C399/A2291).
Glasgow Author(s) Enlighten ID:Evans, Professor Jeff
Authors: Cebon, J. S., Gore, M., Thompson, J. F., Davis, I. D., McArthur, G. A., Walpole, E., Smithers, M., Cerundolo, V., Dunbar, P. R., MacGregor, D., Fisher, C., Millward, M., Nathan, P., Findlay, M. P.N., Hersey, P., Evans, T.R. J., Ottensmeier, C. H., Marsden, J., Dalgleish, A. G., Corrie, P. G., Maria, M., Brimble, M., Williams, G., Winkler, S., Jackson, H. M., Endo-Munoz, L., Tutuka, C. S.A., Venhaus, R., Old, L. J., Haack, D., Maraskovsky, E., Behren, A., and Chen, W.
College/School:College of Medical Veterinary and Life Sciences > School of Cancer Sciences
Journal Name:Journal for ImmunoTherapy of Cancer
Publisher:BMJ Publishing Group
ISSN (Online):2051-1426
Published Online:20 April 2020
Copyright Holders:Copyright © 2020 The Authors
First Published:First published in Journal for ImmunoTherapy of Cancer 8(1): e000410
Publisher Policy:Reproduced under a Creative Commons License

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