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



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
et al (show 23 more authors) (2020) 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. JOURNAL FOR IMMUNOTHERAPY OF CANCER, 8 (1). e000410-.

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Abstract

<h4>Background</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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<sup>+</sup> and CD8<sup>+</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)<sup>+</sup>/Human Leukocyte Antigen (HLA) class I<sup>+</sup> double-positive cells in biopsies from vaccine recipients performed on relapse in 19 participants.<h4>Conclusions</h4>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.

Item Type: Article
Uncontrolled Keywords: oncology, immunology, tumours, randomised trials, HLA
Depositing User: Symplectic Admin
Date Deposited: 21 May 2020 08:59
Last Modified: 21 Jan 2024 13:00
DOI: 10.1136/jitc-2019-000410
Related URLs:
URI: https://livrepository.liverpool.ac.uk/id/eprint/3088188