{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T15:26:26Z","timestamp":1792855586580,"version":"4.5.0"},"reference-count":18,"publisher":"American Medical Association (AMA)","issue":"7","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAMA Netw Open"],"abstract":"\n Importance<\/jats:title>\n The PACIFIC trial established durvalumab as the standard-of-care therapy for unresectable, stage III non\u2013small 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.<\/jats:p>\n <\/jats:sec>\n \n Objective<\/jats:title>\n 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.<\/jats:p>\n <\/jats:sec>\n \n Design, Setting, and Participants<\/jats:title>\n 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.<\/jats:p>\n <\/jats:sec>\n \n Intervention<\/jats:title>\n 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.<\/jats:p>\n <\/jats:sec>\n \n Main Outcomes and Measures<\/jats:title>\n 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.<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n 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\u2009=\u200959), durvalumab plus monalizumab (n\u2009=\u200961), or durvalumab alone (n\u2009=\u200966). 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.<\/jats:p>\n <\/jats:sec>\n \n Conclusions and Relevance<\/jats:title>\n 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.<\/jats:p>\n <\/jats:sec>\n \n Trial Registration<\/jats:title>\n \n ClinicalTrials.gov Identifier:\n NCT03822351<\/jats:ext-link>\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1001\/jamanetworkopen.2025.18440","type":"journal-article","created":{"date-parts":[[2025,7,15]],"date-time":"2025-07-15T15:00:19Z","timestamp":1752591619000},"page":"e2518440","source":"Crossref","is-referenced-by-count":35,"title":["Durvalumab Alone or Combined With Novel Agents for Unresectable Stage III Non\u2013Small Cell Lung Cancer"],"prefix":"10.1001","volume":"8","author":[{"given":"Charu","family":"Aggarwal","sequence":"first","affiliation":[{"name":"Abramson Cancer Center, University of Pennsylvania, Philadelphia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alex","family":"Martinez-Marti","sequence":"additional","affiliation":[{"name":"Vall D\u2019Hebron Institute of Oncology (VHIO), Hospital Universitari Vall D\u2019Hebron, Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Margarita","family":"Majem","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabrice","family":"Barlesi","sequence":"additional","affiliation":[{"name":"Gustave Roussy, Villejuif, France"},{"name":"Paris Saclay University, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Enric","family":"Carcereny","sequence":"additional","affiliation":[{"name":"Institut Catal\u00e0 D\u2019Oncologia, Badalona-Hospital Germans Trias i Pujol, Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Quincy","family":"Chu","sequence":"additional","affiliation":[{"name":"Cross Cancer Institute, Edmonton, Alberta, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isabelle","family":"Monnet","sequence":"additional","affiliation":[{"name":"Department of Pulmonology, Centre Hospitalier Intercommunal de Cr\u00e9teil, Cr\u00e9teil, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alfredo","family":"S\u00e1nchez-Hern\u00e1ndez","sequence":"additional","affiliation":[{"name":"Medical Oncology Department, Consorcio Hospitalario Provincial de Castell\u00f3n, Castell\u00f3n, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shaker","family":"Dakhil","sequence":"additional","affiliation":[{"name":"Cancer Center of Kansas, Wichita"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D. 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