@article {Cebone000410, author = {Jonathan S Cebon and Martin Gore and John F Thompson and Ian D Davis and Grant A McArthur and Euan Walpole and Mark Smithers and Vincenzo Cerundolo and P Rod Dunbar and Duncan MacGregor and Cyril Fisher and Michael Millward and Paul Nathan and Michael P N Findlay and Peter Hersey and T R Jeffry Evans and Christian Hermann Ottensmeier and Jeremy Marsden and Angus G Dalgleish and Pippa G Corrie and Marples Maria and Margaret Brimble and Geoff Williams and Sintia Winkler and Heather M Jackson and Liliana Endo-Munoz and Candani S A Tutuka and Ralph Venhaus and Lloyd J Old and Dennis Haack and Eugene Maraskovsky and Andreas Behren and Weisan Chen}, title = {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}, volume = {8}, number = {1}, elocation-id = {e000410}, year = {2020}, doi = {10.1136/jitc-2019-000410}, publisher = {BMJ Specialist Journals}, abstract = {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.}, URL = {https://jitc.bmj.com/content/8/1/e000410}, eprint = {https://jitc.bmj.com/content/8/1/e000410.full.pdf}, journal = {Journal for ImmunoTherapy of Cancer} }