{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T17:53:29Z","timestamp":1792518809466,"version":"4.5.0"},"reference-count":32,"publisher":"BMJ","issue":"9","license":[{"start":{"date-parts":[[2024,9,30]],"date-time":"2024-09-30T00:00:00Z","timestamp":1727654400000},"content-version":"unspecified","delay-in-days":29,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Bristol-Myers Squibb","award":["CA209-7FP"],"award-info":[{"award-number":["CA209-7FP"]}]},{"DOI":"10.13039\/501100004622","name":"Dutch Cancer Society","doi-asserted-by":"crossref","award":["KWF 14102"],"award-info":[{"award-number":["KWF 14102"]}],"id":[{"id":"10.13039\/501100004622","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["J Immunother Cancer"],"accepted":{"date-parts":[[2024,9,8]]},"published-print":{"date-parts":[[2024,9]]},"abstract":"\n Background<\/jats:title>\n In non-small cell lung cancer (NSCLC), chemoradiotherapy (CRT) yields pathological complete response (pCR) rates of approximately 30%. We investigated using ipilimumab plus nivolumab (IPI-NIVO) with neoadjuvant CRT in resectable, and borderline resectable NSCLC.<\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n This single-arm, phase-II trial enrolled operable T3-4N0\u20132 patients with NSCLC without oncogenic drivers. Primary study endpoints were safety, major pathological response (MPR) and pCR. Treatment encompassed platinum-doublet concurrent CRT, IPI 1\u2009mg\/kg intravenous and NIVO 360\u2009mg intravenous on day-1, followed by chemotherapy plus NIVO 360\u2009mg 3\u2009weeks later. Thoracic radiotherapy was 50 or 60\u2009Gy, in once-daily doses of 2\u2009Gy. Resections were 6\u2009weeks post-radiotherapy.<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n In a total of 30 patients in the intention-to-treat (ITT) population, grades 3\u20134 treatment-related adverse events (TRAEs) occurred in 70%, one TRAE grade 5 late-onset pneumonitis on day 96 post-surgery (1\/30, 3.3%) occurred, and one non-TRAE COVID-19 death (1\/30, 3.3%). pCR and MPR were achieved in 50% (15\/30) and 63% (19\/30) of the ITT; and in 58% (15\/26) and 73% (19\/26) of the 26 patients who underwent surgery, respectively. Postoperative melanoma was seen in one non-pCR patient. The R0 rate was 100% (26\/26), and no patient failed surgery due to TRAEs. In peripheral blood, proliferative CD8\n +<\/jats:sup>\n T cells were increased, while proliferative regulatory T cells (Tregs) were not. On-treatment, pCR-positives had higher CD8\n +<\/jats:sup>\n CD39\n +<\/jats:sup>\n T cells and lower HLA-DR\n +<\/jats:sup>\n Tregs.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n Neoadjuvant IPI-NIVO-CRT in T3-4N0\u20132 NSCLC showed acceptable safety with pCR and MPR in 58% and 73% of operated patients, respectively. No patient failed surgery due to TRAEs.<\/jats:p>\n <\/jats:sec>\n \n Trial registration number<\/jats:title>\n \n NCT04245514<\/jats:ext-link>\n .\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1136\/jitc-2024-009799","type":"journal-article","created":{"date-parts":[[2024,9,30]],"date-time":"2024-09-30T13:25:27Z","timestamp":1727702727000},"page":"e009799","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":22,"title":["Single-arm trial of neoadjuvant ipilimumab plus nivolumab with chemoradiotherapy in patients with resectable and borderline resectable lung cancer: the INCREASE study"],"prefix":"10.1136","volume":"12","clinical-trial-number":[{"clinical-trial-number":"nct04245514","registry":"10.18810\/clinical-trials-gov"},{"clinical-trial-number":"nct03968419","registry":"10.18810\/clinical-trials-gov"},{"clinical-trial-number":"nct03794544","registry":"10.18810\/clinical-trials-gov"},{"clinical-trial-number":"nct03158129","registry":"10.18810\/clinical-trials-gov"},{"clinical-trial-number":"nct04338620","registry":"10.18810\/clinical-trials-gov"},{"clinical-trial-number":"nct02998528","registry":"10.18810\/clinical-trials-gov"},{"clinical-trial-number":"nct03838159","registry":"10.18810\/clinical-trials-gov"},{"clinical-trial-number":"nct03800134","registry":"10.18810\/clinical-trials-gov"},{"clinical-trial-number":"nct04025879","registry":"10.18810\/clinical-trials-gov"},{"clinical-trial-number":"nct03425643","registry":"10.18810\/clinical-trials-gov"},{"clinical-trial-number":"nct04158440","registry":"10.18810\/clinical-trials-gov"},{"clinical-trial-number":"nct04379635","registry":"10.18810\/clinical-trials-gov"}],"author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1111-608X","authenticated-orcid":false,"given":"Idris","family":"Bahce","sequence":"first","affiliation":[{"name":"Department of Pulmonary Medicine, Amsterdam UMC Location VUmc, Amsterdam, Noord-Holland, Netherlands"},{"name":"Imaging and Biomarkers, Cancer Centre Amsterdam, Amsterdam, Noord-Holland, Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chris","family":"Dickhoff","sequence":"additional","affiliation":[{"name":"Department of Cardiothoracic Surgery, Amsterdam UMC location Vrije Universiteit Amsterdam, Amsterdam, Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Famke L","family":"Schneiders","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, Amsterdam UMC location Vrije Universiteit Amsterdam, Amsterdam, Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joris","family":"Veltman","sequence":"additional","affiliation":[{"name":"Department of Pulmonary Medicine, Amsterdam UMC location Vrije Universiteit Amsterdam, Amsterdam, Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David J","family":"Heineman","sequence":"additional","affiliation":[{"name":"Department of Cardiothoracic Surgery, Amsterdam UMC location Vrije Universiteit Amsterdam, Amsterdam, Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sayed M S","family":"Hashemi","sequence":"additional","affiliation":[{"name":"Department of Pulmonary Medicine, location Vrije Universiteit Amsterdam, Amsterdam, Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne","family":"Vrijmoet","sequence":"additional","affiliation":[{"name":"Department of Pulmonary Medicine, Amsterdam UMC location Vrije Universiteit Amsterdam, Amsterdam, Noord-Holland, Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ilias","family":"Houda","sequence":"additional","affiliation":[{"name":"Department of Pulmonary Medicine, Amsterdam UMC location Vrije Universiteit Amsterdam, Amsterdam, Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1551-738X","authenticated-orcid":false,"given":"Ezgi B","family":"Ulas","sequence":"additional","affiliation":[{"name":"Department of Pulmonary Medicine, Amsterdam UMC Locatie VUmc, Amsterdam, Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joyce","family":"Bakker","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Amsterdam UMC location Vrije Universiteit Amsterdam, Amsterdam, Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"van de Ven","sequence":"additional","affiliation":[{"name":"Department of Epidemiology & Biostatistics, Amsterdam UMC location Vrije Universiteit Amsterdam, Amsterdam, Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natalja","family":"Bouwhuis","sequence":"additional","affiliation":[{"name":"Department of Clinical 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