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

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, T. R. Jeffry Evans, Christian Hermann Ottensmeier, Jeremy Marsden, Angus G. Dalgleish, Pippa G. CorrieMarples 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, Weisan Chen

Research output: Contribution to journalArticleResearchpeer-review

16 Citations (Scopus)


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.

Original languageEnglish
Article numbere000410
Number of pages11
JournalJournal for ImmunoTherapy of Cancer
Issue number1
Publication statusPublished - 20 Apr 2020


  • HLA
  • immunology
  • oncology
  • randomised trials
  • tumours

Cite this