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

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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Item Type: Article
Status: Published
Official URL: https://doi.org/10.1136/jitc-2019-000410
Journal or Publication Title: Journal for ImmunoTherapy of Cancer
Volume: 8
Number: 1
Page Range: e000410
Date: 2020
Divisions: Melanoma Oncology and Immunology
Depositing User: General Admin
Identification Number: 10.1136/jitc-2019-000410
ISSN: 2051-1426
Date Deposited: 04 Jan 2021 01:29
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.

Creators:
Creators
Email
Cebon, Jonathan S
UNSPECIFIED
Gore, Martin
UNSPECIFIED
Thompson, John F
UNSPECIFIED
Davis, Ian D
UNSPECIFIED
McArthur, Grant A
UNSPECIFIED
Walpole, Euan
UNSPECIFIED
Smithers, Mark
UNSPECIFIED
Cerundolo, Vincenzo
UNSPECIFIED
Dunbar, P Rod
UNSPECIFIED
MacGregor, Duncan
UNSPECIFIED
Fisher, Cyril
UNSPECIFIED
Millward, Michael
UNSPECIFIED
Nathan, Paul
UNSPECIFIED
Findlay, Michael P N
UNSPECIFIED
Hersey, Peter
UNSPECIFIED
Evans, T R Jeffry
UNSPECIFIED
Ottensmeier, Christian Hermann
UNSPECIFIED
Marsden, Jeremy
UNSPECIFIED
Dalgleish, Angus G
UNSPECIFIED
Corrie, Pippa G
UNSPECIFIED
Maria, Marples
UNSPECIFIED
Brimble, Margaret
UNSPECIFIED
Williams, Geoff
UNSPECIFIED
Winkler, Sintia
UNSPECIFIED
Jackson, Heather M
UNSPECIFIED
Endo-Munoz, Liliana
UNSPECIFIED
Tutuka, Candani S A
UNSPECIFIED
Venhaus, Ralph
UNSPECIFIED
Old, Lloyd J
UNSPECIFIED
Haack, Dennis
UNSPECIFIED
Maraskovsky, Eugene
UNSPECIFIED
Behren, Andreas
UNSPECIFIED
Chen, Weisan
UNSPECIFIED
Last Modified: 04 Jan 2021 01:29
URI: https://eprints.centenary.org.au/id/eprint/781

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