Long-term survival follow-up for tebentafusp in previously treated metastatic uveal melanoma

Background: Tebentafusp, a bispecific (gp100xCD3) ImmTAC, significantly improved overall survival (OS) outcomes for HLA-A*02:01+ adult patients with untreated metastatic uveal melanoma (mUM) and showed promising survival in previously treated mUM with 1-year OS of 62% in the primary analysis of stud...

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Autores: Sacco, Joseph J., Carvajal, Richard D., Butler, Marcus O., Shoushtari, Alexander N., Hassel, Jessica C., Ikeguchi, Alexandra, Hernandez Aya, Leonel, Nathan, Paul, Hamid, Omid, Piulats, Josep M., Rioth, Matthew, Johnson, Douglas B., Luke, Jason J., Espinosa, Enrique, Leyvraz, Serge, Collins, Laura, Holland, Chris, Sato, Takami
Formato: artículo
Fecha de publicación:2024
País:España
Recursos:Universidad de Barcelona
Repositorio:Dipòsit Digital de la UB
OAI Identifier:oai:diposit.ub.edu:2445/214827
Acesso em linha:https://hdl.handle.net/2445/214827
Access Level:acceso abierto
Palavra-chave:Immunoteràpia
Melanoma
Immunotheraphy
id ES_a2fdcc0634b0b28045adcc4aab72e1b6
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repository_id_str
spelling Long-term survival follow-up for tebentafusp in previously treated metastatic uveal melanomaSacco, Joseph J.Carvajal, Richard D.Butler, Marcus O.Shoushtari, Alexander N.Hassel, Jessica C.Ikeguchi, AlexandraHernandez Aya, LeonelNathan, PaulHamid, OmidPiulats, Josep M.Rioth, MatthewJohnson, Douglas B.Luke, Jason J.Espinosa, EnriqueLeyvraz, SergeCollins, LauraHolland, ChrisSato, TakamiImmunoteràpiaMelanomaImmunotheraphyMelanomaBackground: Tebentafusp, a bispecific (gp100xCD3) ImmTAC, significantly improved overall survival (OS) outcomes for HLA-A*02:01+ adult patients with untreated metastatic uveal melanoma (mUM) and showed promising survival in previously treated mUM with 1-year OS of 62% in the primary analysis of study IMCgp100-102. Here we report long-term outcomes from this phase 1/2 study in pretreated mUM. Patients and methods: Patients with previously treated mUM received tebentafusp weekly intravenous at 20 mu g dose 1, 30 mu g dose 2 and either 54, 64, 68, or 73 mu g (phase 1) or 68 mu g (phase 2) dose 3+. The primary objective was overall response rate. Secondary objectives included OS and safety. OS was estimated by Kaplan-Meier methods. Association between OS and baseline covariates, on-treatment Response Evaluation Criteria in Solid Tumors (RECIST) response, baseline tumor biopsy and circulating-tumor DNA (ctDNA) changes were assessed.Results 146 patients were treated with tebentafusp: 19 in phase 1 and 127 in phase 2. With a median follow-up duration of 48.5 months, the median OS was 17.4 months (95% CI, 13.1 to 22.8), and the 1-year, 2-year, 3-year and 4-year OS rates were 62%, 40%, 23% and 14%, respectively. Improved survival was associated with lower ctDNA baseline levels and greater ctDNA reductions by week 9 on-treatment, with 100% 1-year, 73% 2-year and 45% 3-year OS rates for patients with ctDNA clearance. Baseline gp100 expression was not associated with survival, despite more RECIST responses among patients with higher expression. No new safety signals were reported with long-term dosing.Conclusions This study represents the longest follow-up of a Tcell receptor bispecific to date and confirms the durable survival benefits achieved with tebentafusp in previously treated mUM with good tolerability long-term. A role for ctDNA reduction as an early indicator of clinical benefit was again suggested for patients treated with tebentafusp.BMJ2024info:eu-repo/semantics/articleapplication/pdfhttps://hdl.handle.net/2445/214827Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))reponame:Dipòsit Digital de la UBinstname:Universidad de BarcelonaInglésReproducció del document publicat a: https://doi.org/10.1136/jitc-2024-009028Journal for ImmunoTherapy of Cancer, 2024, vol. 12, num. 6, p. e009028https://doi.org/10.1136/jitc-2024-009028cc by-nc (c) Sacco, Joseph J. et al., 2024http://creativecommons.org/licenses/by-nc/3.0/es/info:eu-repo/semantics/openAccessoai:diposit.ub.edu:2445/2148272026-05-27T06:46:51Z
dc.title.none.fl_str_mv Long-term survival follow-up for tebentafusp in previously treated metastatic uveal melanoma
title Long-term survival follow-up for tebentafusp in previously treated metastatic uveal melanoma
spellingShingle Long-term survival follow-up for tebentafusp in previously treated metastatic uveal melanoma
Sacco, Joseph J.
Immunoteràpia
Melanoma
Immunotheraphy
Melanoma
title_short Long-term survival follow-up for tebentafusp in previously treated metastatic uveal melanoma
title_full Long-term survival follow-up for tebentafusp in previously treated metastatic uveal melanoma
title_fullStr Long-term survival follow-up for tebentafusp in previously treated metastatic uveal melanoma
title_full_unstemmed Long-term survival follow-up for tebentafusp in previously treated metastatic uveal melanoma
title_sort Long-term survival follow-up for tebentafusp in previously treated metastatic uveal melanoma
dc.creator.none.fl_str_mv Sacco, Joseph J.
Carvajal, Richard D.
Butler, Marcus O.
Shoushtari, Alexander N.
Hassel, Jessica C.
Ikeguchi, Alexandra
Hernandez Aya, Leonel
Nathan, Paul
Hamid, Omid
Piulats, Josep M.
Rioth, Matthew
Johnson, Douglas B.
Luke, Jason J.
Espinosa, Enrique
Leyvraz, Serge
Collins, Laura
Holland, Chris
Sato, Takami
author Sacco, Joseph J.
author_facet Sacco, Joseph J.
Carvajal, Richard D.
Butler, Marcus O.
Shoushtari, Alexander N.
Hassel, Jessica C.
Ikeguchi, Alexandra
Hernandez Aya, Leonel
Nathan, Paul
Hamid, Omid
Piulats, Josep M.
Rioth, Matthew
Johnson, Douglas B.
Luke, Jason J.
Espinosa, Enrique
Leyvraz, Serge
Collins, Laura
Holland, Chris
Sato, Takami
author_role author
author2 Carvajal, Richard D.
Butler, Marcus O.
Shoushtari, Alexander N.
Hassel, Jessica C.
Ikeguchi, Alexandra
Hernandez Aya, Leonel
Nathan, Paul
Hamid, Omid
Piulats, Josep M.
Rioth, Matthew
Johnson, Douglas B.
Luke, Jason J.
Espinosa, Enrique
Leyvraz, Serge
Collins, Laura
Holland, Chris
Sato, Takami
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Immunoteràpia
Melanoma
Immunotheraphy
Melanoma
topic Immunoteràpia
Melanoma
Immunotheraphy
Melanoma
description Background: Tebentafusp, a bispecific (gp100xCD3) ImmTAC, significantly improved overall survival (OS) outcomes for HLA-A*02:01+ adult patients with untreated metastatic uveal melanoma (mUM) and showed promising survival in previously treated mUM with 1-year OS of 62% in the primary analysis of study IMCgp100-102. Here we report long-term outcomes from this phase 1/2 study in pretreated mUM. Patients and methods: Patients with previously treated mUM received tebentafusp weekly intravenous at 20 mu g dose 1, 30 mu g dose 2 and either 54, 64, 68, or 73 mu g (phase 1) or 68 mu g (phase 2) dose 3+. The primary objective was overall response rate. Secondary objectives included OS and safety. OS was estimated by Kaplan-Meier methods. Association between OS and baseline covariates, on-treatment Response Evaluation Criteria in Solid Tumors (RECIST) response, baseline tumor biopsy and circulating-tumor DNA (ctDNA) changes were assessed.Results 146 patients were treated with tebentafusp: 19 in phase 1 and 127 in phase 2. With a median follow-up duration of 48.5 months, the median OS was 17.4 months (95% CI, 13.1 to 22.8), and the 1-year, 2-year, 3-year and 4-year OS rates were 62%, 40%, 23% and 14%, respectively. Improved survival was associated with lower ctDNA baseline levels and greater ctDNA reductions by week 9 on-treatment, with 100% 1-year, 73% 2-year and 45% 3-year OS rates for patients with ctDNA clearance. Baseline gp100 expression was not associated with survival, despite more RECIST responses among patients with higher expression. No new safety signals were reported with long-term dosing.Conclusions This study represents the longest follow-up of a Tcell receptor bispecific to date and confirms the durable survival benefits achieved with tebentafusp in previously treated mUM with good tolerability long-term. A role for ctDNA reduction as an early indicator of clinical benefit was again suggested for patients treated with tebentafusp.
publishDate 2024
dc.date.none.fl_str_mv 2024
dc.type.none.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv https://hdl.handle.net/2445/214827
url https://hdl.handle.net/2445/214827
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Reproducció del document publicat a: https://doi.org/10.1136/jitc-2024-009028
Journal for ImmunoTherapy of Cancer, 2024, vol. 12, num. 6, p. e009028
https://doi.org/10.1136/jitc-2024-009028
dc.rights.none.fl_str_mv cc by-nc (c) Sacco, Joseph J. et al., 2024
http://creativecommons.org/licenses/by-nc/3.0/es/
info:eu-repo/semantics/openAccess
rights_invalid_str_mv cc by-nc (c) Sacco, Joseph J. et al., 2024
http://creativecommons.org/licenses/by-nc/3.0/es/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv BMJ
publisher.none.fl_str_mv BMJ
dc.source.none.fl_str_mv Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))
reponame:Dipòsit Digital de la UB
instname:Universidad de Barcelona
instname_str Universidad de Barcelona
reponame_str Dipòsit Digital de la UB
collection Dipòsit Digital de la UB
repository.name.fl_str_mv
repository.mail.fl_str_mv
_version_ 1869415343433187328
score 15.811543

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