TY - JOUR T1 - 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 JF - Journal for ImmunoTherapy of Cancer JO - J Immunother Cancer DO - 10.1136/jitc-2019-000410 VL - 8 IS - 1 SP - e000410 AU - Jonathan S Cebon AU - Martin Gore AU - John F Thompson AU - Ian D Davis AU - Grant A McArthur AU - Euan Walpole AU - Mark Smithers AU - Vincenzo Cerundolo AU - P Rod Dunbar AU - Duncan MacGregor AU - Cyril Fisher AU - Michael Millward AU - Paul Nathan AU - Michael P N Findlay AU - Peter Hersey AU - T R Jeffry Evans AU - Christian Hermann Ottensmeier AU - Jeremy Marsden AU - Angus G Dalgleish AU - Pippa G Corrie AU - Marples Maria AU - Margaret Brimble AU - Geoff Williams AU - Sintia Winkler AU - Heather M Jackson AU - Liliana Endo-Munoz AU - Candani S A Tutuka AU - Ralph Venhaus AU - Lloyd J Old AU - Dennis Haack AU - Eugene Maraskovsky AU - Andreas Behren AU - Weisan Chen Y1 - 2020/04/01 UR - http://jitc.bmj.com/content/8/1/e000410.abstract N2 - 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. ER -