{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,10]],"date-time":"2026-11-10T17:15:25Z","timestamp":1794330925557,"version":"4.9.0"},"reference-count":32,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,1,16]],"date-time":"2026-01-16T00:00:00Z","timestamp":1768521600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"},{"start":{"date-parts":[[2026,2,11]],"date-time":"2026-02-11T00:00:00Z","timestamp":1770768000000},"content-version":"vor","delay-in-days":26,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"}],"funder":[{"name":"Innovent Biologics, Shanghai, China"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["BMC Med"],"DOI":"10.1186\/s12916-025-04597-8","type":"journal-article","created":{"date-parts":[[2026,1,16]],"date-time":"2026-01-16T03:55:40Z","timestamp":1768535740000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Safety and preliminary efficacy results of IBI389, an anti-Claudin18.2\u00d7CD3 bispecific antibody, in patients with solid tumors and gastric or gastro-esophageal tumors: a phase 1 dose escalation and expansion study"],"prefix":"10.1186","volume":"24","author":[{"given":"Xiaoyu","family":"Li","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruihong","family":"Dai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qi","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zengqing","family":"Guo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Changlu","family":"Hu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuping","family":"Sun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zuoxing","family":"Niu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jihui","family":"Hao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mingjun","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guanghai","family":"Dai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dong","family":"Hua","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yueyin","family":"Pan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuqing","family":"Wei","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaobing","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qian","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yulong","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jieer","family":"Ying","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Zheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Feng","family":"Bi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,1,16]]},"reference":[{"issue":"23","key":"4597_CR1","doi-asserted-by":"publisher","first-page":"7624","DOI":"10.1158\/1078-0432.CCR-08-1547","volume":"14","author":"U Sahin","year":"2008","unstructured":"Sahin U, Koslowski M, Dhaene K, Usener D, Brandenburg G, Seitz G, et al. Claudin-18 splice variant 2 is a pan-cancer target suitable for therapeutic antibody development. Clin Cancer Res. 2008;14(23):7624\u201334.","journal-title":"Clin Cancer Res"},{"issue":"5","key":"4597_CR2","doi-asserted-by":"publisher","first-page":"3367","DOI":"10.21037\/tcr-19-1876","volume":"9","author":"JY Hong","year":"2020","unstructured":"Hong JY, An JY, Lee J, Park SH, Park JO, Park YS, et al. Claudin 18.2 expression in various tumor types and its role as a potential target in advanced gastric cancer. Transl Cancer Res. 2020;9(5):3367\u201374.","journal-title":"Transl Cancer Res"},{"issue":"12","key":"4597_CR3","doi-asserted-by":"publisher","DOI":"10.1016\/j.esmoop.2024.104000","volume":"9","author":"TY Kim","year":"2024","unstructured":"Kim TY, Kwak Y, Nam SK, Han D, Oh DY, Im SA, et al. Clinicopathological analysis of claudin 18.2 focusing on intratumoral heterogeneity and survival in patients with metastatic or unresectable gastric cancer. ESMO Open. 2024;9(12):104000.","journal-title":"ESMO Open"},{"key":"4597_CR4","doi-asserted-by":"publisher","DOI":"10.3390\/jpm11111095","author":"A Pellino","year":"2021","unstructured":"Pellino A, Brignola S, Riello E, Niero M, Murgioni S, Guido M, et al. Association of CLDN18 protein expression with clinicopathological features and prognosis in advanced gastric and gastroesophageal junction adenocarcinomas. J Pers Med. 2021. https:\/\/doi.org\/10.3390\/jpm11111095.","journal-title":"J Pers Med"},{"key":"4597_CR5","doi-asserted-by":"publisher","DOI":"10.1016\/j.tranon.2025.102362","volume":"55","author":"RJ Arseneau","year":"2025","unstructured":"Arseneau RJ, Kempster E, Bekkers C, Samson T, Gala-Lopez BL, Ramjeesingh R, et al. Claudin 18 (43-14A clone) expression in pancreatic ductal adenocarcinoma: assessment of a potential clinical biomarker for zolbetuximab therapy. Transl Oncol. 2025;55:102362.","journal-title":"Transl Oncol"},{"issue":"9","key":"4597_CR6","doi-asserted-by":"publisher","first-page":"1487","DOI":"10.1093\/annonc\/mdz199","volume":"30","author":"O Tureci","year":"2019","unstructured":"Tureci O, Sahin U, Schulze-Bergkamen H, Zvirbule Z, Lordick F, Koeberle D, et al. A multicentre, phase IIa study of zolbetuximab as a single agent in patients with recurrent or refractory advanced adenocarcinoma of the stomach or lower oesophagus: the MONO study. Ann Oncol. 2019;30(9):1487\u201395.","journal-title":"Ann Oncol"},{"issue":"6","key":"4597_CR7","doi-asserted-by":"publisher","first-page":"1189","DOI":"10.1038\/s41591-022-01800-8","volume":"28","author":"C Qi","year":"2022","unstructured":"Qi C, Gong J, Li J, Liu D, Qin Y, Ge S, et al. Claudin18.2-specific CAR T cells in gastrointestinal cancers: phase 1 trial interim results. Nat Med. 2022;28(6):1189\u201398.","journal-title":"Nat Med"},{"issue":"1","key":"4597_CR8","doi-asserted-by":"publisher","DOI":"10.1186\/s13045-024-01595-w","volume":"17","author":"KI Zhou","year":"2024","unstructured":"Zhou KI, Strickler JH, Chen H. Targeting Claudin-18.2 for cancer therapy: updates from 2024 ASCO annual meeting. J Hematol Oncol. 2024;17(1):73.","journal-title":"J Hematol Oncol"},{"issue":"12","key":"4597_CR9","volume":"16","author":"A Samanta","year":"2024","unstructured":"Samanta A, Ghosh A, Sarma M. Zolbetuximab for unresectable and metastatic gastric and gastroesophageal junction adenocarcinoma: a review of literature. Cureus. 2024;16(12):e75206.","journal-title":"Cureus"},{"issue":"10494","key":"4597_CR10","doi-asserted-by":"publisher","first-page":"2049","DOI":"10.1016\/S0140-6736(25)00860-8","volume":"405","author":"C Qi","year":"2025","unstructured":"Qi C, Liu C, Peng Z, Zhang Y, Wei J, Qiu W, et al. Claudin-18 isoform 2-specific CAR T-cell therapy (satri-cel) versus treatment of physician\u2019s choice for previously treated advanced gastric or gastro-oesophageal junction cancer (CT041-ST-01): a randomised, open-label, phase 2 trial. Lancet. 2025;405(10494):2049\u201360.","journal-title":"Lancet"},{"issue":"10396","key":"4597_CR11","doi-asserted-by":"publisher","first-page":"142","DOI":"10.1016\/S0140-6736(23)00521-4","volume":"402","author":"N van de Donk","year":"2023","unstructured":"van de Donk N, Zweegman S. T-cell-engaging bispecific antibodies in cancer. Lancet. 2023;402(10396):142\u201358.","journal-title":"Lancet"},{"issue":"9","key":"4597_CR12","doi-asserted-by":"publisher","first-page":"e693","DOI":"10.1016\/S2352-3026(24)00186-8","volume":"11","author":"N van de Donk","year":"2024","unstructured":"van de Donk N, Chari A, Mateos MV. Mechanisms of resistance against T-cell engaging bispecific antibodies in multiple myeloma: implications for novel treatment strategies. Lancet Haematol. 2024;11(9):e693-707.","journal-title":"Lancet Haematol"},{"issue":"1","key":"4597_CR13","doi-asserted-by":"publisher","DOI":"10.1093\/immadv\/ltae005","volume":"5","author":"L Dewaele","year":"2025","unstructured":"Dewaele L, Fernandes RA. Bispecific T-cell engagers for the recruitment of T cells in solid tumors: a literature review. Immunother Adv. 2025;5(1):ltae005.","journal-title":"Immunother Adv"},{"key":"4597_CR14","doi-asserted-by":"publisher","DOI":"10.3390\/antib8030043","author":"Q Wang","year":"2019","unstructured":"Wang Q, Chen Y, Park J, Liu X, Hu Y, Wang T, et al. Design and production of bispecific antibodies. Antibodies. 2019. https:\/\/doi.org\/10.3390\/antib8030043.","journal-title":"Antibodies"},{"key":"4597_CR15","doi-asserted-by":"publisher","DOI":"10.3390\/biom10030399","author":"A Yoon","year":"2020","unstructured":"Yoon A, Lee S, Lee S, Lim S, Park YY, Song E, et al. A novel T cell-engaging bispecific antibody for treating mesothelin-positive solid tumors. Biomolecules. 2020. https:\/\/doi.org\/10.3390\/biom10030399.","journal-title":"Biomolecules"},{"issue":"6026","key":"4597_CR16","doi-asserted-by":"publisher","first-page":"354","DOI":"10.1038\/316354a0","volume":"316","author":"P Perez","year":"1985","unstructured":"Perez P, Hoffman RW, Shaw S, Bluestone JA, Segal DM. Specific targeting of cytotoxic T cells by anti-T3 linked to anti-target cell antibody. Nature. 1985;316(6026):354\u20136.","journal-title":"Nature"},{"issue":"6","key":"4597_CR17","doi-asserted-by":"publisher","first-page":"539","DOI":"10.4161\/mabs.1.6.10015","volume":"1","author":"P Chames","year":"2009","unstructured":"Chames P, Baty D. Bispecific antibodies for cancer therapy: the light at the end of the tunnel? MAbs. 2009;1(6):539\u201347.","journal-title":"MAbs"},{"issue":"3","key":"4597_CR18","doi-asserted-by":"publisher","first-page":"321","DOI":"10.1007\/s40265-015-0356-3","volume":"75","author":"M Sanford","year":"2015","unstructured":"Sanford M. Blinatumomab: first global approval. Drugs. 2015;75(3):321\u20137.","journal-title":"Drugs"},{"issue":"9","key":"4597_CR19","doi-asserted-by":"publisher","first-page":"836","DOI":"10.1056\/NEJMoa1609783","volume":"376","author":"H Kantarjian","year":"2017","unstructured":"Kantarjian H, Stein A, Gokbuget N, Fielding AK, Schuh AC, Ribera JM, et al. Blinatumomab versus chemotherapy for advanced acute lymphoblastic leukemia. N Engl J Med. 2017;376(9):836\u201347.","journal-title":"N Engl J Med"},{"issue":"18","key":"4597_CR20","doi-asserted-by":"publisher","first-page":"1959","DOI":"10.1200\/JCO.20.03175","volume":"39","author":"M Hutchings","year":"2021","unstructured":"Hutchings M, Morschhauser F, Iacoboni G, Carlo-Stella C, Offner FC, Sureda A, et al. Glofitamab, a novel, bivalent CD20-targeting T-cell-engaging bispecific antibody, induces durable complete remissions in relapsed or refractory B-cell lymphoma: a phase I trial. J Clin Oncol. 2021;39(18):1959\u201370.","journal-title":"J Clin Oncol"},{"issue":"12","key":"4597_CR21","doi-asserted-by":"publisher","first-page":"2238","DOI":"10.1200\/JCO.22.01725","volume":"41","author":"C Thieblemont","year":"2023","unstructured":"Thieblemont C, Phillips T, Ghesquieres H, Cheah CY, Clausen MR, Cunningham D, et al. Epcoritamab, a novel, subcutaneous CD3xCD20 bispecific T-cell-engaging antibody, in relapsed or refractory large B-cell lymphoma: dose expansion in a phase I\/II trial. J Clin Oncol. 2023;41(12):2238\u201347.","journal-title":"J Clin Oncol"},{"issue":"24","key":"4597_CR22","doi-asserted-by":"publisher","first-page":"2220","DOI":"10.1056\/NEJMoa2206913","volume":"387","author":"MJ Dickinson","year":"2022","unstructured":"Dickinson MJ, Carlo-Stella C, Morschhauser F, Bachy E, Corradini P, Iacoboni G, et al. Glofitamab for relapsed or refractory diffuse large B-cell lymphoma. N Engl J Med. 2022;387(24):2220\u201331.","journal-title":"N Engl J Med"},{"issue":"16","key":"4597_CR23","doi-asserted-by":"publisher","first-page":"2893","DOI":"10.1200\/JCO.22.02823","volume":"41","author":"L Paz-Ares","year":"2023","unstructured":"Paz-Ares L, Champiat S, Lai WV, Izumi H, Govindan R, Boyer M, et al. Tarlatamab, a first-in-class DLL3-targeted bispecific T-cell engager, in recurrent small-cell lung cancer: an open-label, phase I study. J Clin Oncol. 2023;41(16):2893\u2013903.","journal-title":"J Clin Oncol"},{"issue":"7","key":"4597_CR24","first-page":"487","volume":"23","author":"A Mullard","year":"2024","unstructured":"Mullard A. FDA approves first DLL3 x CD3 bispecific T-cell engager for lung cancer. Nat Rev Drug Discov. 2024;23(7):487.","journal-title":"Nat Rev Drug Discov"},{"key":"4597_CR25","unstructured":"Assay VC-A: Access date: May 5, 2025. https:\/\/elabdoc-prod.roche.com\/eLD\/api\/downloads\/ff8f8fc9-3536-ea11-fc90-005056a71a5d?countryIsoCode=XG."},{"key":"4597_CR26","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejca.2024.114075","volume":"205","author":"A Geraud","year":"2024","unstructured":"Geraud A, Hueso T, Laparra A, Bige N, Ouali K, Cauquil C, et al. Reactions and adverse events induced by T-cell engagers as anti-cancer immunotherapies, a comprehensive review. Eur J Cancer. 2024;205:114075.","journal-title":"Eur J Cancer"},{"key":"4597_CR27","doi-asserted-by":"publisher","DOI":"10.3390\/cancers16030679","author":"MC Mathias-Machado","year":"2024","unstructured":"Mathias-Machado MC, de Jesus VHF, Jacome A, Donadio MD, Aruquipa MPS, Fogacci J, et al. Claudin 18.2 as a new biomarker in gastric cancer-what should we know? Cancers (Basel). 2024. https:\/\/doi.org\/10.3390\/cancers16030679.","journal-title":"Cancers (Basel)"},{"issue":"6","key":"4597_CR28","doi-asserted-by":"publisher","first-page":"1431","DOI":"10.21037\/jgo-20-344","volume":"11","author":"B Xu","year":"2020","unstructured":"Xu B, Liu F, Liu Q, Shi T, Wang Z, Wu N, et al. Highly expressed claudin18.2 as a potential therapeutic target in advanced gastric signet-ring cell carcinoma (SRCC). J Gastrointest Oncol. 2020;11(6):1431\u20139.","journal-title":"J Gastrointest Oncol"},{"issue":"3","key":"4597_CR29","doi-asserted-by":"publisher","first-page":"1035","DOI":"10.21037\/jgo-22-462","volume":"13","author":"W Weng","year":"2022","unstructured":"Weng W, Zhang M, Ni S, Tan C, Xu M, Wang X, et al. Decreased expression of claudin-18.2 in alpha-fetoprotein-producing gastric cancer compared to conventional gastric cancer. J Gastrointest Oncol. 2022;13(3):1035\u201345.","journal-title":"J Gastrointest Oncol"},{"key":"4597_CR30","doi-asserted-by":"publisher","DOI":"10.1186\/s12957-015-0626-2","volume":"13","author":"JX Liu","year":"2015","unstructured":"Liu JX, Wei ZY, Chen JS, Lu HC, Hao L, Li WJ. Prognostic and clinical significance of claudin-4 in gastric cancer: a meta-analysis. World J Surg Oncol. 2015;13:207.","journal-title":"World J Surg Oncol"},{"key":"4597_CR31","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2021.643872","volume":"11","author":"BS Ungureanu","year":"2021","unstructured":"Ungureanu BS, Lungulescu CV, Pirici D, Turcu-Stiolica A, Gheonea DI, Sacerdotianu VM, et al. Clinicopathologic relevance of claudin 18.2 expression in gastric cancer: a meta-analysis. Front Oncol. 2021;11:643872.","journal-title":"Front Oncol"},{"issue":"2","key":"4597_CR32","doi-asserted-by":"publisher","first-page":"227","DOI":"10.1016\/S1470-2045(24)00636-3","volume":"26","author":"DY Ruan","year":"2025","unstructured":"Ruan DY, Liu FR, Wei XL, Luo SX, Zhuang ZX, Wang ZN, et al. Claudin 18.2-targeting antibody-drug conjugate CMG901 in patients with advanced gastric or gastro-oesophageal junction cancer (KYM901): a multicentre, open-label, single-arm, phase 1 trial. Lancet Oncol. 2025;26(2):227\u201338.","journal-title":"Lancet Oncol"}],"container-title":["BMC Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s12916-025-04597-8","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12916-025-04597-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12916-025-04597-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,2,11]],"date-time":"2026-02-11T17:45:16Z","timestamp":1770831916000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1186\/s12916-025-04597-8"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1,16]]},"references-count":32,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,12]]}},"alternative-id":["4597"],"URL":"https:\/\/doi.org\/10.1186\/s12916-025-04597-8","relation":{},"ISSN":["1741-7015"],"issn-type":[{"value":"1741-7015","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1,16]]},"assertion":[{"value":"30 July 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"18 December 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"16 January 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"This study was initially approved by the Ethics Committee of West China Hospital, Sichuan University. The study was conducted in strict accordance with the protocol and adhered to the principles of the Declaration of Helsinki, and other relevant laws and regulations. Written informed consent was obtained from all participants prior to the initiation of any study-specific procedures.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"Qian Wu, Yulong Zhang, and Hui Zhou reported being employees of Innovent Biologics (Suzhou) Co. Ltd. Other authors declare no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"91"}}