Please use this identifier to cite or link to this item: https://ahro.austin.org.au/austinjspui/handle/1/23075
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.
Austin Authors: 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;Jackson, Heather M;Endo-Munoz, Liliana;Tutuka, Candani S A;Venhaus, Ralph;Old, Lloyd J;Haack, Dennis;Maraskovsky, Eugene;Behren, Andreas;Chen, Weisan
Affiliation: School of Cancer Medicine, La Trobe University at Austin Health, Heidelberg, Victoria, Australia
Monash University Eastern Health Clinical School, Box Hill, Victoria, Australia
Melanona and Skin Service, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia
Cancer Services Division, Princess Alexandra Hospital Health Service District, Woolloongabba, Queensland, Australia
Oncology Services Unit, Princess Alexandra Hospital Health Service District, Woolloongabba, Queensland, Australia
Department of Anatomical Pathology, Austin Health, Heidelberg, Victoria, Australia
School of Medicine and Pharmacology, Sir Charles Gairdner Hospital, Nedlands, Western Australia, Australia
Melanoma Immunology and Oncology Group, Centenary Institute, Newtown, New South Wales, Australia
Ludwig Institute for Cancer Research, Austin Health, Heidelberg, Victoria, Australia
CSL Limited, Melbourne, Victoria, Australia
Oncology, Royal Marsden Hospital NHS Trust, London, UK
Melanoma Institute Australia, North Sydney, New South Wales, Australia
Ludwig Institute for Cancer Research, New York, New York, USA
Versagenics Inc, Morrisville, North Carolina, USA
Biochemistry and Genetics, La Trobe University, Melbourne, Victoria, Australia
School of Cancer Medicine, La Trobe University at Austin Health, Heidelberg, Victoria, Australia
MRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, Oxford, Oxfordshire, UK
School of Biological Sciences and Maurice Wilkins Centre, The University of Auckland, Auckland, New Zealand
Oncology, Royal Marsden Hospital NHS Trust, London, UK
Mount Vernon Cancer Centre, Mount Vernon Hospital, Northwood, London, UK
School of Medicine and Health Science, The University of Auckland, Auckland, New Zealand
Institute of Cancer Sciences, University of Glasgow, Glasgow, UK
School of Cancer Sciences, University of Southampton Faculty of Medicine, Southampton, Hampshire, UK
University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK
Cell and Molecular Sciences, Division of Oncology, St Georges Hospital Medical School, London, UK
West Anglia Cancer Research Network Oncology Centre, Addenbrooke's Hospital, Cambridge, Cambridgeshire, UK
The Cancer Research Centre, Weston Park Hospital, Sheffield, UK
School of Biological Sciences and Maurice Wilkins Centre, The University of Auckland, Auckland, New Zealand
Cancer Immunobiology Programme, Olivia Newton-John Cancer Research Institute, Heidelberg, Victoria, Australia
Issue Date: Apr-2020
Publication information: Journal for immunotherapy of cancer 2020; 8(1): e000410
Abstract: 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. 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. 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. 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.
URI: http://ahro.austin.org.au/austinjspui/handle/1/23075
DOI: 10.1136/jitc-2019-000410
ORCID: 0000-0002-3898-950X
0000-0002-2816-2496
0000-0002-9066-8244
0000-0001-8908-6071
0000-0001-6105-9039
0000-0002-8333-8685
0000-0001-9626-2600
0000-0002-3305-9768
0000-0002-3064-737X
0000-0002-4175-914X
0000-0003-3619-1657
0000-0003-4875-7021
0000-0002-7086-4096
0000-0001-5329-280X
0000-0002-5221-9771
PubMed URL: 32317292
Type: Journal Article
Subjects: HLA
immunology
oncology
randomised trials
tumours
Appears in Collections:Journal articles

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