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Cebon, Jonathan S; Gore, Martin; Thompson, John F; Davis, Ian D; McArthur, Grant A; Walpole, Euan; Smithers, Mark; Cerundolo, Vincenzo; Dunbar, P Rod; MacGregor, Duncan; Fisher, Cyril; Millward, Michael; Nathan, Paul; Findlay, Michael P N; Hersey, Peter; Evans, T R Jeffry; Ottensmeier, Christian Hermann; Marsden, Jeremy; Dalgleish, Angus G; Corrie, Pippa G; Maria, Marples; Brimble, Margaret; Williams, Geoff; Winkler, Sintia; [...]

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

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  • Media type: E-Article
  • 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
  • Contributor: Cebon, Jonathan S; Gore, Martin; Thompson, John F; Davis, Ian D; McArthur, Grant A; Walpole, Euan; Smithers, Mark; Cerundolo, Vincenzo; Dunbar, P Rod; MacGregor, Duncan; Fisher, Cyril; Millward, Michael; Nathan, Paul; Findlay, Michael P N; Hersey, Peter; Evans, T R Jeffry; Ottensmeier, Christian Hermann; Marsden, Jeremy; Dalgleish, Angus G; Corrie, Pippa G; Maria, Marples; Brimble, Margaret; Williams, Geoff; Winkler, Sintia; [...]
  • imprint: BMJ, 2020
  • Published in: Journal for ImmunoTherapy of Cancer
  • Language: English
  • DOI: 10.1136/jitc-2019-000410
  • ISSN: 2051-1426
  • Origination:
  • Footnote:
  • Description: <jats:sec><jats:title>Background</jats:title><jats:p>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.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>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.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>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<jats:sup>+</jats:sup>and CD8<jats:sup>+</jats:sup>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)<jats:sup>+</jats:sup>/Human Leukocyte Antigen (HLA) class I<jats:sup>+</jats:sup>double-positive cells in biopsies from vaccine recipients performed on relapse in 19 participants.</jats:p></jats:sec><jats:sec><jats:title>Conclusions</jats:title><jats:p>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.</jats:p></jats:sec>
  • Access State: Open Access