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Association of homogeneous inflamed gene signature with a better outcome in patients with metastatic melanoma treated with MAGE-A3 immunotherapeutic

PURPOSE: This study assessed clinical activity, safety and immunogenicity of MAGE-A3 immunotherapeutic in patients with MAGE-A3-positive metastatic melanoma. PATIENTS AND METHODS: In this open-label, multicentre, uncontrolled, Phase II study (ClinicalTrials.gov NCT00896480), patients received ≤24 do...

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Autores principales: Baurain, Jean-François, Robert, Caroline, Mortier, Laurent, Neyns, Bart, Grange, Florent, Lebbe, Céleste, Ulloa-Montoya, Fernando, De Sousa Alves, Pedro Miguel, Gillet, Marc, Louahed, Jamila, Jarnjak, Silvija, Lehmann, Frédéric F
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BMJ Publishing Group 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6069918/
https://www.ncbi.nlm.nih.gov/pubmed/30094070
http://dx.doi.org/10.1136/esmoopen-2018-000384
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author Baurain, Jean-François
Robert, Caroline
Mortier, Laurent
Neyns, Bart
Grange, Florent
Lebbe, Céleste
Ulloa-Montoya, Fernando
De Sousa Alves, Pedro Miguel
Gillet, Marc
Louahed, Jamila
Jarnjak, Silvija
Lehmann, Frédéric F
author_facet Baurain, Jean-François
Robert, Caroline
Mortier, Laurent
Neyns, Bart
Grange, Florent
Lebbe, Céleste
Ulloa-Montoya, Fernando
De Sousa Alves, Pedro Miguel
Gillet, Marc
Louahed, Jamila
Jarnjak, Silvija
Lehmann, Frédéric F
author_sort Baurain, Jean-François
collection PubMed
description PURPOSE: This study assessed clinical activity, safety and immunogenicity of MAGE-A3 immunotherapeutic in patients with MAGE-A3-positive metastatic melanoma. PATIENTS AND METHODS: In this open-label, multicentre, uncontrolled, Phase II study (ClinicalTrials.gov NCT00896480), patients received ≤24 doses of MAGE-A3 immunotherapeutic (4-cycle schedule). At screening, two skin lesions were biopsied for MAGE-A3 expression analysis and presence/absence of a previously identified gene signature (GS) associated with favourable clinical outcome. Clinical activity was assessed in terms of clinical response, time-to-treatment failure (TTF) and progression-free survival (PFS). Adverse events (AEs) and serious AEs (SAEs) were recorded. MAGE-A3-specific immune responses were assessed. Clinical activity and immunogenicity were analysed overall and separately in patients with 2/2 (GS+/+), 1/2 (GS+/-) or 0/2 (GS-/-) biopsies presenting GS. RESULTS: Of 49 screened patients, 32 had MAGE-A3-positive tumours; 24 (8 GS+/+, 8 GS+/-, 8 GS-/-) were treated. Two complete (GS+/+ patients) and two partial responses (one GS+/+, one GS+/-) were reported; of note, one of the two complete responses was unlikely to be related to the study treatment. Median TTF and PFS were 14.8 and 7.2 months for GS+/+, 2.3 and 2.8 months for GS+/- and 2.4 and 2.9 months for GS-/- patients. Three grade 3 AEs and two SAEs unrelated to treatment were reported. All patients were seropositive for MAGE-A3 antibodies on vaccination with no differences between the different GS profiles. MAGE-A3-specific CD4+ and CD8+ T cell immunogenicity was detected; 12/16 (75.0%) of patients presented CD4+ T cell responses. CONCLUSION: Treatment with MAGE-A3 immunotherapeutic showed signs of clinical activity in GS+/+ patients. Treatment was well tolerated and immunogenic. No differences in immune responses according to GS status were observed. TRIAL REGISTRATION NUMBER: NCT00896480 (Results).
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spelling pubmed-60699182018-08-09 Association of homogeneous inflamed gene signature with a better outcome in patients with metastatic melanoma treated with MAGE-A3 immunotherapeutic Baurain, Jean-François Robert, Caroline Mortier, Laurent Neyns, Bart Grange, Florent Lebbe, Céleste Ulloa-Montoya, Fernando De Sousa Alves, Pedro Miguel Gillet, Marc Louahed, Jamila Jarnjak, Silvija Lehmann, Frédéric F ESMO Open Original Research PURPOSE: This study assessed clinical activity, safety and immunogenicity of MAGE-A3 immunotherapeutic in patients with MAGE-A3-positive metastatic melanoma. PATIENTS AND METHODS: In this open-label, multicentre, uncontrolled, Phase II study (ClinicalTrials.gov NCT00896480), patients received ≤24 doses of MAGE-A3 immunotherapeutic (4-cycle schedule). At screening, two skin lesions were biopsied for MAGE-A3 expression analysis and presence/absence of a previously identified gene signature (GS) associated with favourable clinical outcome. Clinical activity was assessed in terms of clinical response, time-to-treatment failure (TTF) and progression-free survival (PFS). Adverse events (AEs) and serious AEs (SAEs) were recorded. MAGE-A3-specific immune responses were assessed. Clinical activity and immunogenicity were analysed overall and separately in patients with 2/2 (GS+/+), 1/2 (GS+/-) or 0/2 (GS-/-) biopsies presenting GS. RESULTS: Of 49 screened patients, 32 had MAGE-A3-positive tumours; 24 (8 GS+/+, 8 GS+/-, 8 GS-/-) were treated. Two complete (GS+/+ patients) and two partial responses (one GS+/+, one GS+/-) were reported; of note, one of the two complete responses was unlikely to be related to the study treatment. Median TTF and PFS were 14.8 and 7.2 months for GS+/+, 2.3 and 2.8 months for GS+/- and 2.4 and 2.9 months for GS-/- patients. Three grade 3 AEs and two SAEs unrelated to treatment were reported. All patients were seropositive for MAGE-A3 antibodies on vaccination with no differences between the different GS profiles. MAGE-A3-specific CD4+ and CD8+ T cell immunogenicity was detected; 12/16 (75.0%) of patients presented CD4+ T cell responses. CONCLUSION: Treatment with MAGE-A3 immunotherapeutic showed signs of clinical activity in GS+/+ patients. Treatment was well tolerated and immunogenic. No differences in immune responses according to GS status were observed. TRIAL REGISTRATION NUMBER: NCT00896480 (Results). BMJ Publishing Group 2018-07-25 /pmc/articles/PMC6069918/ /pubmed/30094070 http://dx.doi.org/10.1136/esmoopen-2018-000384 Text en © European Society for Medical Oncology 2018. Re-use permitted under CC BY-NC. No commercial re-use. Published by BMJ. This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/.
spellingShingle Original Research
Baurain, Jean-François
Robert, Caroline
Mortier, Laurent
Neyns, Bart
Grange, Florent
Lebbe, Céleste
Ulloa-Montoya, Fernando
De Sousa Alves, Pedro Miguel
Gillet, Marc
Louahed, Jamila
Jarnjak, Silvija
Lehmann, Frédéric F
Association of homogeneous inflamed gene signature with a better outcome in patients with metastatic melanoma treated with MAGE-A3 immunotherapeutic
title Association of homogeneous inflamed gene signature with a better outcome in patients with metastatic melanoma treated with MAGE-A3 immunotherapeutic
title_full Association of homogeneous inflamed gene signature with a better outcome in patients with metastatic melanoma treated with MAGE-A3 immunotherapeutic
title_fullStr Association of homogeneous inflamed gene signature with a better outcome in patients with metastatic melanoma treated with MAGE-A3 immunotherapeutic
title_full_unstemmed Association of homogeneous inflamed gene signature with a better outcome in patients with metastatic melanoma treated with MAGE-A3 immunotherapeutic
title_short Association of homogeneous inflamed gene signature with a better outcome in patients with metastatic melanoma treated with MAGE-A3 immunotherapeutic
title_sort association of homogeneous inflamed gene signature with a better outcome in patients with metastatic melanoma treated with mage-a3 immunotherapeutic
topic Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6069918/
https://www.ncbi.nlm.nih.gov/pubmed/30094070
http://dx.doi.org/10.1136/esmoopen-2018-000384
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