• Jonathan S Cebon, Martin Gore, John F Thompson, Ian D Davis, Grant A McArthur, Euan Walpole, Mark Smithers, Vincenzo Cerundolo, P Rod Dunbar, Duncan MacGregor, Cyril Fisher, Michael Millward, Paul Nathan, Michael P N Findlay, Peter Hersey, EvansT R JeffryTRJ0000-0002-4175-914XInstitute of Cancer Sciences, University of Glasgow, Glasgow, UK., Christian Hermann Ottensmeier, Jeremy Marsden, Angus G Dalgleish, Pippa G Corrie, Marples Maria, Margaret Brimble, Geoff Williams, Sintia Winkler, Heather M Jackson, Liliana Endo-Munoz, Candani S A Tutuka, Ralph Venhaus, Lloyd J Old, Dennis Haack, Eugene Maraskovsky, Andreas Behren, and Weisan Chen.
• Cancer Immunobiology Programme, Olivia Newton-John Cancer Research Institute, School of Cancer Medicine, La Trobe University at Austin Health, Heidelberg, Victoria, Australia j.cebon@onjcri.org.au.
• J Immunother Cancer. 2020 Apr 1; 8 (1).

BackgroundTo 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.MethodsParticipants 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.ResultsThe 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.ConclusionsThe 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.© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

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