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Here we report on stage 1, which aimed to confirm the dose and assess the preliminary efficacy (primary outcome: overall survival; secondary outcomes: progression\u2011free survival, objective response rate and duration of response) and safety of gotistobart compared to docetaxel. Patients with sqNSCLC were randomized (1:1) to gotistobart (6\u2009mg\u2009kg\n                    <jats:sup>\u22121<\/jats:sup>\n                    with two 10\u2009mg\u2009kg\n                    <jats:sup>\u22121<\/jats:sup>\n                    loading doses every 3\u2009weeks (\n                    <jats:italic>N<\/jats:italic>\n                    \u2009=\u200945)) or docetaxel (75\u2009mg\u2009m\n                    <jats:sup>\u2212<\/jats:sup>\n                    <jats:sup>2<\/jats:sup>\n                    every 3 weeks (\n                    <jats:italic>N<\/jats:italic>\n                    \u2009=\u200942)). After a median follow-up of 14.5\u2009months, median overall survival was not reached with gotistobart (95% confidence interval (CI) 9.3 to not evaluable) versus 10.0\u2009months (95% CI 6.2 to 11.9\u2009months) with docetaxel (hazard ratio 0.46, 95% CI 0.25 to 0.84, nominal two-sided\n                    <jats:italic>P<\/jats:italic>\n                    \u2009=\u20090.0102). Safety was manageable, with grade \u22653 treatment-related adverse events in 42% and 49% of patients receiving gotistobart and docetaxel, respectively. Stage 1 results suggest that gotistobart monotherapy can provide clinically meaningful benefit for patients with programmed cell death protein\/programmed death ligand 1-resistant and chemotherapy-resistant metastatic sqNSCLC. ClinicalTrials.gov identifier:\n                    <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"https:\/\/clinicaltrials.gov\/search?term=NCT05671510\" ext-link-type=\"uri\">NCT05671510<\/jats:ext-link>\n                    .\n                  <\/jats:p>","DOI":"10.1038\/s41591-026-04323-8","type":"journal-article","created":{"date-parts":[[2026,3,27]],"date-time":"2026-03-27T14:02:47Z","timestamp":1774620167000},"page":"2245-2253","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Gotistobart or docetaxel in metastatic squamous non-small cell lung cancer: stage 1 of the randomized phase 3 PRESERVE-003 trial"],"prefix":"10.1038","volume":"32","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5562-270X","authenticated-orcid":false,"given":"Byoung 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B.C. has been an invited speaker for ASCO, AstraZeneca, ESMO, Guardant, IASLC, Korean Cancer Association, Korean Cancer Study Group, Korean Society of Medical Oncology, Korean Society of Thyroid-Head and Neck Surgery, MSD, Novartis, Pfizer, Roche, The Chinese Thoracic Oncology Society and Zailab; has participated on advisory boards for Bridgebio, Cyrus Therapeutics, Guardant, J INTS Bio, KANAPH Therapeutic Inc. and Therapex; has consulted for Amgen, ArriVent, AstraZeneca, AnHeart Therapeutics, BeiGene, BMS, Boehringer-Ingelheim, CJ, Cyrus Therapeutics, Daiichi Sankyo, Eli Lilly, Gilead, GSK, Harpoon Therapeutics, Janssen, MSD, Novartis, Ono Pharmaceuticals, Pfizer, Regeneron, Roche, Sanofi, Seagen, Takeda and Yuhan; has received research support from AstraZeneca, Champions Oncology, CJ Bioscience, Cyrus Therapeutics, Dong-A ST, GIInnovation, ImmuneOncia, Janssen, J INTS Bio, MSD, Vertical Bio AG and Therapex; is Founder of DAAN Biotherapeutics; is a Member of Board of Directors for JIINTSBio; is an employee of Yonsei University Health System; and has equity in Bridgebio Therapeutics, Champions Oncology, Crown Bioscience, Cyrus Therapeutics, Gencurix Inc, Imagen, Interpark Bio Convergence Corp., J INTS Bio, KANAPH Therapeutic Inc., PearlRiver Bio GmbH and TheraCanVax Inc. H.C. is Principal Investigator (PI) at Guangdong University. J.Z. is the Coordinating PI at Chengdu Seventh People\u2019s Hospital. Long Wu is the Coordinating PI at Renmin Hospital of Wuhan University. J.L. has been an invited speaker for AstraZeneca, BMS, Dragonfly Therapeutics, Guardant Health, Imugene, Iovance Biotherapeutics, Merck, OncLive and OncoC4 Inc.; and has served on advisory boards for AstraZeneca and Jazz Pharmaceuticals. J.H. has received research support from BioNTech SE. Y.H. is the PI at Hainan General Hospital. K.H.L. has consulted for Amgen, AstraZeneca, BMS, Boehringer-Ingelheim, Daiichi Sankyo, Eli Lilly, Janssen, Merck, MSD, Pfizer, Takeda and Yuhan; and has received research support from Merck and Ono Pharmaceuticals. Y.J.L. has consulted for Amgen, AstraZeneca, Bayer, Merck, Roche and Yuhan. X.W. is PI at The First Affiliated Hospital of Guangdong Pharmaceutical University. M.S. is the PI at Jinan Central Hospital; has been an invited speaker for AstraZeneca, Genentech, Guardant, Janssen, Jazz Pharmaceuticals, Nuvation and Regeneron Pharmaceuticals; has participated on advisory boards and steering committees for AstraZeneca, BeiOne, BMS, Merck, OncoC4 Inc. and Summit; and has received research support from BeiOne, Eli Lilly, Enliven, Genentech and Nuvation. S.E. is an employee of OncoC4 Inc. S. Shpyro is an employee of BioNTech SE. Q.W. is an employee of BioNTech SE. M.W. is an employee of BioNTech SE. U.\u015e. is co-founder, a management board member and employee of BioNTech SE and holds securities from BioNTech SE. S. Song is an employee of OncoC4 Inc. P.Z. is co-founder, board member and Chief Medical Officer of OncoC4 Inc., and has an ownership interest in OncoC4 Inc. Y. Liu is co-founder, board member and Chief Executive Officer of OncoC4 Inc., and has an ownership interest in OncoC4 Inc. Kai He has been an invited speaker for Amgen, Beigene, BioNTech SE, BMS, Genentech, GSK, Iovance, Iyell, Mirati, Obsidian, OncoC4 Inc., Servier and Synthekine; and has participated on advisory boards for Amgen, AstraZeneca, Beigene, BioNTech SE, BMS, Iovance, Lyell, Mirati, Obsidian, Regeneron Pharmaceuticals and Synthekine. T.L. has served on advisory boards for AstraZeneca and Regeneron Pharmaceuticals and has received research support from Amgen, AstraZeneca, BioNTech SE, BMS, Chugai Pharmaceutical Co., Duality Biologics, Genentech, LabyRx Immunologic Therapeutics, Marengo Therapeutics, OncoC4 Inc., RasCal Therapeutics, Regeneron Pharmaceuticals, Tempus and Xilio Therapeutics. All other authors report no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}]}}