Durvalumab Alone or Combined With Novel Agents for Unresectable Stage III Non-Small Cell Lung Cancer Update From the COAST Randomized Clinical Trial

IMPORTANCE The PACIFIC trial established durvalumab as the standard-of-care therapy for unresectable, stage III non-small cell lung cancer (NSCLC) without progression following concurrent chemoradiotherapy (cCRT). Novel immunotherapy combinations involving the anti-CD73 monoclonal antibody oleclumab...

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Authors: Aggarwal, Charu|||0000-0002-3181-9460, Martinez-Marti, Alex|||0000-0002-6714-9526, Majem Tarruella, Margarita|||0000-0002-9919-7485, Barlesi, Fabrice, Carcereny, Enric|||0000-0001-5235-5602, Chu, Quincy|||0000-0003-4814-3126, Monnet, Isabelle, Sánchez Hernández, Alfredo|||0000-0001-5826-8390, Dakhil, Shaker, Cooper, Zachary A.|||0000-0003-1059-0940, Kumar, Rakesh|||0000-0002-4627-3667, Herbst, Roy S.|||0000-0003-2535-5847, Camidge, D.|||0000-0003-3430-3213, Pillet, Marine, Brown, Miranda, Paliompeis, Christos, Dowson, Adam
Format: article
Publication Date:2025
Country:España
Institution:Universitat Autònoma de Barcelona
Repository:Dipòsit Digital de Documents de la UAB
Language:English
OAI Identifier:oai:dnet:uabarcelona_::cc7d1dfeda0508a41e78ead9488c9b39
Online Access:https://ddd.uab.cat/record/326788
https://dx.doi.org/urn:doi:10.1001/jamanetworkopen.2025.18440
Access Level:Open access
Keyword:Adult
Aged
Aged, 80 and over
Antibodies, Monoclonal
Antibodies, Monoclonal, Humanized
Antineoplastic Agents, Immunological
Antineoplastic Combined Chemotherapy Protocols
Carcinoma, Non-Small-Cell Lung
Female
Humans
Lung Neoplasms
Male
Middle Aged
Neoplasm Staging
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oai_identifier_str oai:dnet:uabarcelona_::cc7d1dfeda0508a41e78ead9488c9b39
network_acronym_str ES
network_name_str España
repository_id_str
dc.title.none.fl_str_mv Durvalumab Alone or Combined With Novel Agents for Unresectable Stage III Non-Small Cell Lung Cancer Update From the COAST Randomized Clinical Trial
title Durvalumab Alone or Combined With Novel Agents for Unresectable Stage III Non-Small Cell Lung Cancer Update From the COAST Randomized Clinical Trial
spellingShingle Durvalumab Alone or Combined With Novel Agents for Unresectable Stage III Non-Small Cell Lung Cancer Update From the COAST Randomized Clinical Trial
Aggarwal, Charu|||0000-0002-3181-9460
Adult
Aged
Aged, 80 and over
Antibodies, Monoclonal
Antibodies, Monoclonal, Humanized
Antineoplastic Agents, Immunological
Antineoplastic Combined Chemotherapy Protocols
Carcinoma, Non-Small-Cell Lung
Female
Humans
Lung Neoplasms
Male
Middle Aged
Neoplasm Staging
title_short Durvalumab Alone or Combined With Novel Agents for Unresectable Stage III Non-Small Cell Lung Cancer Update From the COAST Randomized Clinical Trial
title_full Durvalumab Alone or Combined With Novel Agents for Unresectable Stage III Non-Small Cell Lung Cancer Update From the COAST Randomized Clinical Trial
title_fullStr Durvalumab Alone or Combined With Novel Agents for Unresectable Stage III Non-Small Cell Lung Cancer Update From the COAST Randomized Clinical Trial
title_full_unstemmed Durvalumab Alone or Combined With Novel Agents for Unresectable Stage III Non-Small Cell Lung Cancer Update From the COAST Randomized Clinical Trial
title_sort Durvalumab Alone or Combined With Novel Agents for Unresectable Stage III Non-Small Cell Lung Cancer Update From the COAST Randomized Clinical Trial
dc.creator.none.fl_str_mv Aggarwal, Charu|||0000-0002-3181-9460
Martinez-Marti, Alex|||0000-0002-6714-9526
Majem Tarruella, Margarita|||0000-0002-9919-7485
Barlesi, Fabrice
Carcereny, Enric|||0000-0001-5235-5602
Chu, Quincy|||0000-0003-4814-3126
Monnet, Isabelle
Sánchez Hernández, Alfredo|||0000-0001-5826-8390
Dakhil, Shaker
Cooper, Zachary A.|||0000-0003-1059-0940
Kumar, Rakesh|||0000-0002-4627-3667
Herbst, Roy S.|||0000-0003-2535-5847
Camidge, D.|||0000-0003-3430-3213
Pillet, Marine
Brown, Miranda
Paliompeis, Christos
Dowson, Adam
author Aggarwal, Charu|||0000-0002-3181-9460
author_facet Aggarwal, Charu|||0000-0002-3181-9460
Martinez-Marti, Alex|||0000-0002-6714-9526
Majem Tarruella, Margarita|||0000-0002-9919-7485
Barlesi, Fabrice
Carcereny, Enric|||0000-0001-5235-5602
Chu, Quincy|||0000-0003-4814-3126
Monnet, Isabelle
Sánchez Hernández, Alfredo|||0000-0001-5826-8390
Dakhil, Shaker
Cooper, Zachary A.|||0000-0003-1059-0940
Kumar, Rakesh|||0000-0002-4627-3667
Herbst, Roy S.|||0000-0003-2535-5847
Camidge, D.|||0000-0003-3430-3213
Pillet, Marine
Brown, Miranda
Paliompeis, Christos
Dowson, Adam
author_role author
author2 Martinez-Marti, Alex|||0000-0002-6714-9526
Majem Tarruella, Margarita|||0000-0002-9919-7485
Barlesi, Fabrice
Carcereny, Enric|||0000-0001-5235-5602
Chu, Quincy|||0000-0003-4814-3126
Monnet, Isabelle
Sánchez Hernández, Alfredo|||0000-0001-5826-8390
Dakhil, Shaker
Cooper, Zachary A.|||0000-0003-1059-0940
Kumar, Rakesh|||0000-0002-4627-3667
Herbst, Roy S.|||0000-0003-2535-5847
Camidge, D.|||0000-0003-3430-3213
Pillet, Marine
Brown, Miranda
Paliompeis, Christos
Dowson, Adam
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Universitat Autònoma de Barcelona. Departament de Medicina
dc.subject.none.fl_str_mv Adult
Aged
Aged, 80 and over
Antibodies, Monoclonal
Antibodies, Monoclonal, Humanized
Antineoplastic Agents, Immunological
Antineoplastic Combined Chemotherapy Protocols
Carcinoma, Non-Small-Cell Lung
Female
Humans
Lung Neoplasms
Male
Middle Aged
Neoplasm Staging
topic Adult
Aged
Aged, 80 and over
Antibodies, Monoclonal
Antibodies, Monoclonal, Humanized
Antineoplastic Agents, Immunological
Antineoplastic Combined Chemotherapy Protocols
Carcinoma, Non-Small-Cell Lung
Female
Humans
Lung Neoplasms
Male
Middle Aged
Neoplasm Staging
description IMPORTANCE The PACIFIC trial established durvalumab as the standard-of-care therapy for unresectable, stage III non-small cell lung cancer (NSCLC) without progression following concurrent chemoradiotherapy (cCRT). Novel immunotherapy combinations involving the anti-CD73 monoclonal antibody oleclumab or the anti-NKG2A monoclonal antibody monalizumab have the potential to build on the durvalumab standard of care. OBJECTIVE To report updated results from the phase 2 COAST trial of consolidation durvalumab alone or combined with oleclumab or monalizumab in patients with unresectable, stage III NSCLC and no progression following cCRT. DESIGN, SETTING, AND PARTICIPANTS COAST was an open-label, phase 2, multidrug platform randomized clinical trial conducted across 73 sites globally. Patients with an Eastern Cooperative Oncology Group Performance Status of 0 or 1 and no progression following definitive platinum-based cCRT were enrolled between January 2019 and July 2020. The data cutoff for this final analysis was July 18, 2023. Data were analyzed from September 2023 to March 2024. INTERVENTION Patients were randomized 1:1:1, stratified by histologic type within 42 days after cCRT, to durvalumab alone or durvalumab combined with oleclumab or monalizumab for up to 12 months. MAIN OUTCOMES AND MEASURES The primary end point was investigator-assessed confirmed objective response rate (ORR). Key secondary end points included investigator-assessed progression-free survival (PFS), overall survival (OS), and safety. Efficacy end points were assessed in the intention-to-treat population. Safety was assessed in the as-treated population. RESULTS Of 189 randomized patients (median [range] age, 65 [37-87] years; 129 males [68.3%]; 176 [93.1%] current or former smokers), 186 received treatment consisting of durvalumab plus oleclumab (n = 59), durvalumab plus monalizumab (n = 61), or durvalumab alone (n = 66). Of these patients, 1 (0.5%) self-reported as American Indian or Alaska Native, 14 (7.5%) as Asian, 8 (4.3%) as Black or African American, 1 (0.5%) as Native Hawaiian or Other Pacific Islander, 159 (85.5%) as White, and 3 (1.6%) as other race. After a median (range) follow-up in all patients of 30.1 (0.4-48.9) months, confirmed ORR was numerically higher with durvalumab plus oleclumab (35.0%; 95% CI, 23.1%-48.4%) or monalizumab (40.3%; 95% CI, 28.1%-53.6%) than with durvalumab alone (23.9%; 95% CI, 14.3%-35.9%). However, the difference in ORR for durvalumab plus oleclumab (11.1 [-6.4 to 28.1] percentage points) and durvalumab plus monalizumab (16.9 [-0.8 to 33.4] percentage points) was not statistically significant compared with durvalumab alone. Both combinations prolonged PFS vs durvalumab alone (plus oleclumab: hazard ratio [HR], 0.59 [95% CI, 0.37-0.93]; plus monalizumab: HR, 0.63 [95% CI, 0.40-0.99]) but did not demonstrate nominal associations with longer OS (plus oleclumab: HR, 0.69 [95% CI, 0.40-1.20]; plus monalizumab: HR, 0.77 [95% CI, 0.44-1.33]). Safety was comparable across arms, without new or notable safety signals. CONCLUSIONS AND RELEVANCE In the COAST trial, combining consolidation durvalumab with oleclumab or monalizumab provided additional clinical benefit over durvalumab alone. This finding supports further investigation of these novel combinations in the phase 3 PACIFIC-9 trial.
publishDate 2025
dc.date.none.fl_str_mv 2
2025-01-01
2025
2025-01-01
dc.type.none.fl_str_mv Article
http://purl.org/coar/resource_type/c_6501
VoR
http://purl.org/coar/version/c_970fb48d4fbd8a85
dc.type.openaire.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv https://ddd.uab.cat/record/326788
https://dx.doi.org/urn:doi:10.1001/jamanetworkopen.2025.18440
url https://ddd.uab.cat/record/326788
https://dx.doi.org/urn:doi:10.1001/jamanetworkopen.2025.18440
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
https://creativecommons.org/licenses/by-nc-nd/4.0/
dc.rights.openaire.fl_str_mv info:eu-repo/semantics/openAccess
rights_invalid_str_mv open access
http://purl.org/coar/access_right/c_abf2
https://creativecommons.org/licenses/by-nc-nd/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.source.none.fl_str_mv reponame:Dipòsit Digital de Documents de la UAB
instname:Universitat Autònoma de Barcelona
instname_str Universitat Autònoma de Barcelona
reponame_str Dipòsit Digital de Documents de la UAB
collection Dipòsit Digital de Documents de la UAB
repository.name.fl_str_mv
repository.mail.fl_str_mv
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spelling Durvalumab Alone or Combined With Novel Agents for Unresectable Stage III Non-Small Cell Lung Cancer Update From the COAST Randomized Clinical TrialAggarwal, Charu|||0000-0002-3181-9460Martinez-Marti, Alex|||0000-0002-6714-9526Majem Tarruella, Margarita|||0000-0002-9919-7485Barlesi, FabriceCarcereny, Enric|||0000-0001-5235-5602Chu, Quincy|||0000-0003-4814-3126Monnet, IsabelleSánchez Hernández, Alfredo|||0000-0001-5826-8390Dakhil, ShakerCooper, Zachary A.|||0000-0003-1059-0940Kumar, Rakesh|||0000-0002-4627-3667Herbst, Roy S.|||0000-0003-2535-5847Camidge, D.|||0000-0003-3430-3213Pillet, MarineBrown, MirandaPaliompeis, ChristosDowson, AdamAdultAgedAged, 80 and overAntibodies, MonoclonalAntibodies, Monoclonal, HumanizedAntineoplastic Agents, ImmunologicalAntineoplastic Combined Chemotherapy ProtocolsCarcinoma, Non-Small-Cell LungFemaleHumansLung NeoplasmsMaleMiddle AgedNeoplasm StagingIMPORTANCE The PACIFIC trial established durvalumab as the standard-of-care therapy for unresectable, stage III non-small cell lung cancer (NSCLC) without progression following concurrent chemoradiotherapy (cCRT). Novel immunotherapy combinations involving the anti-CD73 monoclonal antibody oleclumab or the anti-NKG2A monoclonal antibody monalizumab have the potential to build on the durvalumab standard of care. OBJECTIVE To report updated results from the phase 2 COAST trial of consolidation durvalumab alone or combined with oleclumab or monalizumab in patients with unresectable, stage III NSCLC and no progression following cCRT. DESIGN, SETTING, AND PARTICIPANTS COAST was an open-label, phase 2, multidrug platform randomized clinical trial conducted across 73 sites globally. Patients with an Eastern Cooperative Oncology Group Performance Status of 0 or 1 and no progression following definitive platinum-based cCRT were enrolled between January 2019 and July 2020. The data cutoff for this final analysis was July 18, 2023. Data were analyzed from September 2023 to March 2024. INTERVENTION Patients were randomized 1:1:1, stratified by histologic type within 42 days after cCRT, to durvalumab alone or durvalumab combined with oleclumab or monalizumab for up to 12 months. MAIN OUTCOMES AND MEASURES The primary end point was investigator-assessed confirmed objective response rate (ORR). Key secondary end points included investigator-assessed progression-free survival (PFS), overall survival (OS), and safety. Efficacy end points were assessed in the intention-to-treat population. Safety was assessed in the as-treated population. RESULTS Of 189 randomized patients (median [range] age, 65 [37-87] years; 129 males [68.3%]; 176 [93.1%] current or former smokers), 186 received treatment consisting of durvalumab plus oleclumab (n = 59), durvalumab plus monalizumab (n = 61), or durvalumab alone (n = 66). Of these patients, 1 (0.5%) self-reported as American Indian or Alaska Native, 14 (7.5%) as Asian, 8 (4.3%) as Black or African American, 1 (0.5%) as Native Hawaiian or Other Pacific Islander, 159 (85.5%) as White, and 3 (1.6%) as other race. After a median (range) follow-up in all patients of 30.1 (0.4-48.9) months, confirmed ORR was numerically higher with durvalumab plus oleclumab (35.0%; 95% CI, 23.1%-48.4%) or monalizumab (40.3%; 95% CI, 28.1%-53.6%) than with durvalumab alone (23.9%; 95% CI, 14.3%-35.9%). However, the difference in ORR for durvalumab plus oleclumab (11.1 [-6.4 to 28.1] percentage points) and durvalumab plus monalizumab (16.9 [-0.8 to 33.4] percentage points) was not statistically significant compared with durvalumab alone. Both combinations prolonged PFS vs durvalumab alone (plus oleclumab: hazard ratio [HR], 0.59 [95% CI, 0.37-0.93]; plus monalizumab: HR, 0.63 [95% CI, 0.40-0.99]) but did not demonstrate nominal associations with longer OS (plus oleclumab: HR, 0.69 [95% CI, 0.40-1.20]; plus monalizumab: HR, 0.77 [95% CI, 0.44-1.33]). Safety was comparable across arms, without new or notable safety signals. CONCLUSIONS AND RELEVANCE In the COAST trial, combining consolidation durvalumab with oleclumab or monalizumab provided additional clinical benefit over durvalumab alone. This finding supports further investigation of these novel combinations in the phase 3 PACIFIC-9 trial.Universitat Autònoma de Barcelona. Departament de Medicina 22025-01-0120252025-01-01Articlehttp://purl.org/coar/resource_type/c_6501VoRhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleapplication/pdfhttps://ddd.uab.cat/record/326788https://dx.doi.org/urn:doi:10.1001/jamanetworkopen.2025.18440reponame:Dipòsit Digital de Documents de la UABinstname:Universitat Autònoma de BarcelonaInglésengopen accesshttp://purl.org/coar/access_right/c_abf2Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, i la comunicació pública de l'obra, sempre que no sigui amb finalitats comercials, i sempre que es reconegui l'autoria de l'obra original. No es permet la creació d'obres derivades.https://creativecommons.org/licenses/by-nc-nd/4.0/info:eu-repo/semantics/openAccessoai:dnet:uabarcelona_::cc7d1dfeda0508a41e78ead9488c9b392026-06-06T12:50:31Z
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