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After repeat genetic testing, therapy was changed to lorlatinib, again leading to early progression. Subsequent treatment with ivonescimab combined with chemotherapy produced a favorable clinical response, representing the first reported ivonescimab use in this specific ALK-TKI–resistant setting and offering reference value for personalized management.",{"@graph":69,"@context":122},[70,84,105],{"@type":71,"itemListElement":72},"BreadcrumbList",[73,77,79,82],{"item":74,"name":75,"@type":76,"position":8},"https://docshare.wps.com","Home","ListItem",{"item":78,"name":9,"@type":76,"position":14},"https://docshare.wps.com/document/",{"item":80,"name":35,"@type":76,"position":81},"https://docshare.wps.com/document/healthcare/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/ivonescimab-combined-with-chemotherapy-shows-promising-efficacy-in-an-alk-fusion-positive-lung-adenocarcinoma-patient-with-alk-tki-resistance-a-case-report/409717/",{"url":83,"name":65,"@type":85,"image":86,"author":91,"headline":65,"publisher":94,"fileFormat":97,"inLanguage":63,"description":67,"dateModified":98,"datePublished":99,"encodingFormat":97,"isAccessibleForFree":100,"interactionStatistic":101},"DigitalDocument",{"url":87,"@type":88,"width":89,"height":90},"https://docshare.wps.com/thumbnails/ivonescimab-combined-with-chemotherapy-shows-promising-efficacy-in-an-alk-fusion-positive-lung-adenocarcinoma-patient-with-alk-tki-resistance-a-case-report/409717.png","ImageObject",300,407,{"name":92,"@type":93},"Asher","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-11-01","2026-09-28",true,{"@type":102,"interactionType":103,"userInteractionCount":24},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"What molecular features were identified in the patient’s lung adenocarcinoma?","Question",{"text":112,"@type":113},"The case described an EML4–ALK fusion, high PD-L1 expression (TPS 75%), and a BIM deletion polymorphism.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"How did the patient respond to alectinib and lorlatinib?",{"text":117,"@type":113},"The patient experienced rapid progression after initial alectinib treatment and again showed early progression after switching to lorlatinib.",{"name":119,"@type":110,"acceptedAnswer":120},"What treatment led to a favorable clinical response in this case?",{"text":121,"@type":113},"Ivonescimab combined with chemotherapy achieved a favorable clinical response after ALK-TKI resistance.","https://schema.org",{"og:url":83,"og:type":124,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":126,"canonical":83},"index,follow",{"doc_id":128,"site_id":62},409717,1790789958,{"code":4,"msg":5,"data":131},{"doc_id":128,"user_id":132,"nickname":92,"user_avatar":133,"doc_module":4,"category_id":34,"category_name":35,"doc_title":65,"doc_description":67,"doc_content":134,"file_id":135,"file_url":136,"file_type":137,"file_size":138,"view_count":24,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":39,"language":139,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":140,"faqs":141,"seo_title":142,"seo_description":67,"update_tm":143,"read_time":46,"preview_page_count":4},687197207639,"https://ap-avatar.wpscdn.com/davatar_a8503ba1806abce46bf441b54a3ca4cd","TYPE Case Report  \nPUBLISHED 18 December 2025 DOI 10.3389/fonc.2025.1723763  \nOPEN ACCESS  \nEDITED BY  \nJames C. M. Ho,  \nThe University of Hong Kong, Hong Kong SAR, China  \nREVIEWED BY  \nRita Leporati,  \nUniversity of Modena and Reggio Emilia, Italy Roland Leung,  \nQueen Mary Hospital, Hong Kong SAR, China  \n*CORRESPONDENCE  \nJun Deng  \n [dj2882@sina.com](dj2882@sina.com)  \n†These authors have contributed equally to this work and share first authorship  \nRECEIVED 13 October 2025  \nREVISED 27 November 2025  \nACCEPTED 04 December 2025  \nPUBLISHED 18 December 2025  \nCITATION  \nLin M, Gao Y and Deng J (2025) Ivonescimab combined with chemotherapy shows promising efficacy in an ALK fusion-positive lung adenocarcinoma patient with ALK-TKI resistance: a case report.  \nFront. Oncol. 15:1723763 .  \ndoi: 10.3389/fonc.2025.1723763  \nCOPYRIGHT  \n© 2025 Lin, Gao and Deng. This is an openaccess article distributed under the terms of the Creative Commons Attribution License (CC BY) . The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.  \nIvonescimab combined with chemotherapy shows promising efficacy in an ALK fusion-positive lung adenocarcinoma patient with ALK-TKI resistance: a case report  \nMeiyuan Lin †, Yuan Gao † and Jun Deng*  \nDepartment of Respiratory and Critical Care Medicine, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, China  \nThis report describes a case of lung adenocarcinoma harboring an echinoderm microtubule-associated protein-like 4–anaplastic lymphoma kinase (EML4–ALK) fusion, high programmed death-ligand 1 (PD-L1) expression, and a Bcl-2-like protein 11 (BIM) deletion polymorphism. The patient was initially treated with alectinib, but experienced rapid disease progression. After repeat genetic testing, therapy was switched to lorlatinib, which again resulted in early progression. Subsequently, treatment with ivonescimab combined with chemotherapy achieved a favorable clinical response. To our knowledge, this is the first reported case of ivonescimab use in such a patient. This case offers a potential reference for the management of ALK fusion–positive lung adenocarcinoma resistant to ALK tyrosine kinase inhibitors (ALK-TKIs) .  \nKEYWORDS  \nivonescimab, non–small cell lung cancer, ALK fusion, drug resistance, BIM deletion polymorphism, case report  \nIntroduction  \nLung cancer poses a serious threat to human health and remains the leading cause of cancer-related deaths worldwide. Approximately 60% of patients with lung adenocarcinoma harbor driver gene alterations, and about 2%–7% of these cases exhibit anaplastic lymphoma kinase (ALK) fusions (1) . For patients with advanced non–small cell lung cancer (NSCLC) harboring ALK fusions, targeted therapy has become the standard first-line treatment, including first-generation (e.g., crizotinib), second-generation (e.g., alectinib), and third-generation (e.g., lorlatinib) ALK tyrosine kinase inhibitors (ALKTKIs) (2–5). Although the use ofALK-TKIs has significantly improved clinical outcomes in this population, the inevitable emergence of drug resistance remains a major clinical challenge (6) . Therefore, identifying effective subsequent treatment strategies for ALK  \nFrontiers in Oncology 01 [frontiersin.org](frontiersin.org)  \nfusion–positive NSCLC patients who experience disease progression after ALK-TKI therapy has become a key focus of current research.  \nWe report a rare case of ALK fusion–positive lung adenocarcinoma with concurrent high programmed death-ligand 1 (PD-L1) expression and a Bcl-2-like protein 11 (BIM) deletion polymorphism. The patient exhibited resistance to both secondand third-generation ALK-TKIs but achieved a sustained clinical response to ivonescimab co","cbCaikBuGnbXao6h","https://ap.wps.com/l/cbCaikBuGnbXao6h","pdf",10482131,"English","# Introduction\n# Case presentation","[{\"question\":\"What molecular features were identified in the patient’s lung adenocarcinoma?\",\"answer\":\"The case described an EML4–ALK fusion, high PD-L1 expression (TPS 75%), and a BIM deletion polymorphism.\"},{\"question\":\"How did the patient respond to alectinib and lorlatinib?\",\"answer\":\"The patient experienced rapid progression after initial alectinib treatment and again showed early progression after switching to lorlatinib.\"},{\"question\":\"What treatment led to a favorable clinical response in this case?\",\"answer\":\"Ivonescimab combined with chemotherapy achieved a favorable clinical response after ALK-TKI resistance.\"}]","Ivonescimab combined with chemotherapy shows promising efficacy in an ALK fusion-positive lung adenocarcinoma patient with ALK-TKI resistance - a case report | PDF",1790582996]