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When given before curative surgery, tumor responses and improved event-free survival are achieved. New antibody combinations may be more efficacious and tolerable. In an ongoing, open-label phase 2 study, 60 biomarker-unselected, treatment-naive patients with resectable non-small-cell lung cancer were randomized to receive two preoperative doses of nivolumab (anti-PD-1) with or without relatlimab (anti-LAG-3) antibody therapy. The primary study endpoint was the feasibility of surgery within 43\u2009days, which was met by all patients. Curative resection was achieved in 95% of patients. Secondary endpoints included pathological and radiographic response rates, pathologically complete resection rates, disease-free and overall survival rates, and safety. Major pathological (\u226410% viable tumor cells) and objective radiographic responses were achieved in 27% and 10% (nivolumab) and in 30% and 27% (nivolumab and relatlimab) of patients, respectively. 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This study establishes the feasibility and safety of dual targeting of PD-1 and LAG-3 before lung cancer surgery.<\/jats:p>\n                  <jats:p>\n                    ClinicalTrials.gov Indentifier:\n                    <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"https:\/\/clinicaltrials.gov\/ct2\/show\/NCT04205552\">NCT04205552<\/jats:ext-link>\n                    .\n                  <\/jats:p>","DOI":"10.1038\/s41591-024-02965-0","type":"journal-article","created":{"date-parts":[[2024,4,30]],"date-time":"2024-04-30T06:01:33Z","timestamp":1714456893000},"page":"1602-1611","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":87,"title":["Neoadjuvant nivolumab with or without relatlimab in resectable non-small-cell lung cancer: a randomized phase 2 trial"],"prefix":"10.1038","volume":"30","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2166-3394","authenticated-orcid":false,"given":"Martin","family":"Schuler","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8153-0008","authenticated-orcid":false,"given":"Kristof","family":"Cuppens","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Till","family":"Pl\u00f6nes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9698-9559","authenticated-orcid":false,"given":"Marcel","family":"Wiesweg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bert","family":"Du Pont","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Balazs","family":"Hegedus","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9818-9320","authenticated-orcid":false,"given":"Johannes","family":"K\u00f6ster","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabian","family":"Mairinger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0681-1325","authenticated-orcid":false,"given":"Kaid","family":"Darwiche","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1651-1262","authenticated-orcid":false,"given":"Annette","family":"Paschen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-2301-3370","authenticated-orcid":false,"given":"Brigitte","family":"Maes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michel","family":"Vanbockrijck","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9138-4112","authenticated-orcid":false,"given":"David","family":"L\u00e4hnemann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2746-9242","authenticated-orcid":false,"given":"Fang","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3581-5264","authenticated-orcid":false,"given":"Hubertus","family":"Hautzel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dirk","family":"Theegarten","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Koen","family":"Hartemink","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henning","family":"Reis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7018-9556","authenticated-orcid":false,"given":"Paul","family":"Baas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7670-7529","authenticated-orcid":false,"given":"Alexander","family":"Schramm","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7787-991X","authenticated-orcid":false,"given":"Clemens","family":"Aigner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,4,30]]},"reference":[{"key":"2965_CR1","doi-asserted-by":"crossref","first-page":"209","DOI":"10.3322\/caac.21660","volume":"71","author":"H Sung","year":"2021","unstructured":"Sung, H. et al. 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The following authors declare potential conflicts of interest: M.S. (Fees for consulting from Amgen, AstraZeneca, Blueprint Medicines, Boehringer Ingelheim, Bristol Myers Squibb, GSK, Janssen, MSD, Novartis, Roche, Sanofi and Tacalyx; honoraria for CME presentations from Amgen, Bristol Myers Squibb, GSK, Janssen, MSD, Roche and Sanofi; institutional research funding to University Hospital Essen from AstraZeneca, Bristol Myers Squibb and Janssen); K.C. (Fees for consulting from AstraZeneca\/Medimmune, Bayer, Bristol Myers Squibb, MSD; institutional research funding from Bristol Myers Squibb; travel support from MSD; other relationship to Bristol Myers Squibb); M.W. (Fees for consulting from Daiichi Sankyo, Janssen, Novartis, Pfizer and Roche; honoraria for CME presentations from Amgen, AstraZeneca, GSK, Janssen, Novartis, Roche and Takeda; institutional research funding to University Hospital Essen from Bristol Myers Squibb and Takeda; travel support from Amgen and Bristol Myers Squibb), B.H. (institutional research funding to University Hospital Essen from Bristol Myers Squibb), K.D. (Fees for consulting from bess, Boehringer Ingelheim, Boston Scientific, Broncus Medical, FreeFlow, Fujifilm, Lys Medical, Medtronic, Morair Medtech, Olympus, Pulmonx and Storz; honoraria for CME presentations from AstraZeneca, Boehringer Ingelheim, Boston Scientific, Broncus Medical, Erbe Elektromedizin, Olympus and Storz; institutional research funding to University Medicine Essen \u2013 Ruhrlandklinik from Ambu, Broncus Medical, Epigenomics, Gala Therapeutics, Novartis, Nuvaira, PneumRx, Pulmonx and Roche); H.H. (Honoraria for CME presentations from Urenco; travel support from Pari; institutional research funding to University Hospital Essen from Pari), H.R. (Honoraria for CME presentations from AstraZeneca, Bristol Myers Squibb, Boehringer Ingelheim, Chop GmbH, Diaceutics, GSK, HUeG, Janssen-Cilag, MCI, Merck, Novartis, Roche Pharma, Sanofi and Wolfsburg Klinikum; institutional research funding from Bristol Myers Squibb), P.B. (Fees for consulting from AstraZeneca, Beigene, Bristol Myers Squibb, Merck Sharp & Dohme; honoraria from Bristol Myers Squibb, MSD; research funding to the Netherlands Cancer Institute from Bristol Myers Squibb; travel support from MSD; other relationship to Bristol Myers Squibb), A.S. (Institutional research funding to University Hospital Essen from Bristol Myers Squibb) and C.A. (Fees for consulting from Ewimed; honoraria for CME presentations from AstraZeneca, Bristol Myers Squibb, Roche; institutional research funding to University Hospital Essen Bristol Myers Squibb, and to University Medicine Essen \u2013 Ruhrlandklinik from PharmaCept). The other authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}]}}