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PBF-1129, an oral selective A2B adenosine receptor antagonist, was evaluated in a Phase 1 open-label dose-escalation study in advanced/metastatic NSCLC after progression on standard therapies. Twenty-one patients received 40–320 mg once daily with no dose-limiting toxicities, dose-proportional pharmacokinetics, and systemic immune modulation.",{"@graph":14,"@context":73},[15,34,56],{"@type":16,"itemListElement":17},"BreadcrumbList",[18,23,27,31],{"item":19,"name":20,"@type":21,"position":22},"https://docshare.wps.com","Home","ListItem",1,{"item":24,"name":25,"@type":21,"position":26},"https://docshare.wps.com/document/","Document",2,{"item":28,"name":29,"@type":21,"position":30},"https://docshare.wps.com/document/healthcare/","Healthcare",3,{"item":32,"name":10,"@type":21,"position":33},"https://docshare.wps.com/document/phase-1-dose-escalation-trial-of-the-selective-adenosine-a2b-antagonist-pbf-1129-in-patients-with-metastatic-non-small-cell-lung-cancer/407473/",4,{"url":32,"name":10,"@type":35,"image":36,"author":41,"headline":10,"publisher":44,"fileFormat":47,"inLanguage":8,"description":12,"dateModified":48,"datePublished":49,"encodingFormat":47,"isAccessibleForFree":50,"interactionStatistic":51},"DigitalDocument",{"url":37,"@type":38,"width":39,"height":40},"https://docshare.wps.com/thumbnails/phase-1-dose-escalation-trial-of-the-selective-adenosine-a2b-antagonist-pbf-1129-in-patients-with-metastatic-non-small-cell-lung-cancer/407473.png","ImageObject",300,407,{"name":42,"@type":43},"Connor ","Person",{"url":19,"name":45,"@type":46},"DocShare","Organization","application/pdf","2026-10-31","2026-09-28",true,{"@type":52,"interactionType":53,"userInteractionCount":55},"InteractionCounter",{"@type":54},"ViewAction",11,{"@type":57,"mainEntity":58},"FAQPage",[59,65,69],{"name":60,"@type":61,"acceptedAnswer":62},"What does the study evaluate?","Question",{"text":63,"@type":64},"The trial evaluates PBF-1129, an oral selective A2B adenosine receptor antagonist, in metastatic non-small cell lung cancer patients using a Phase 1 dose-escalation design.","Answer",{"name":66,"@type":61,"acceptedAnswer":67},"How was dosing administered and what safety signal was observed?",{"text":68,"@type":64},"Patients received escalating once-daily doses of 40–320 mg. No dose-limiting toxicities were observed.",{"name":70,"@type":61,"acceptedAnswer":71},"What biological and clinical responses were reported?",{"text":72,"@type":64},"Pharmacokinetics were dose-proportional with plasma concentrations above IC90 at 320 mg for 24 hours. Stable disease occurred in some patients, and post-treatment reductions in PD-1 expression on CD8+ T cells correlated with improved survival.","https://schema.org",{"og:url":32,"og:type":75,"og:title":10,"og:site_name":45,"og:description":12},"article",{"robots":77,"canonical":32},"index,follow",{"doc_id":79,"site_id":7},407473,1790804961,{"code":4,"msg":82,"data":83},"success",[84,88,92,96,101,106,110,115,120,123,127],{"id":22,"doc_module":4,"doc_module_name":25,"category_name":85,"show_sort_weight":86,"slug":87},"Story & Novel",90,"story-novel",{"id":26,"doc_module":4,"doc_module_name":25,"category_name":89,"show_sort_weight":90,"slug":91},"Literature",80,"literature",{"id":33,"doc_module":4,"doc_module_name":25,"category_name":93,"show_sort_weight":94,"slug":95},"Exam",70,"exam",{"id":97,"doc_module":4,"doc_module_name":25,"category_name":98,"show_sort_weight":99,"slug":100},5,"Comic",60,"comic",{"id":102,"doc_module":4,"doc_module_name":25,"category_name":103,"show_sort_weight":104,"slug":105},6,"Technology",50,"technology",{"id":107,"doc_module":4,"doc_module_name":25,"category_name":29,"show_sort_weight":108,"slug":109},7,40,"healthcare",{"id":111,"doc_module":4,"doc_module_name":25,"category_name":112,"show_sort_weight":113,"slug":114},8,"Research & Report",30,"research-report",{"id":116,"doc_module":4,"doc_module_name":25,"category_name":117,"show_sort_weight":118,"slug":119},9,"Religion & Spirituality",20,"religion-spirituality",{"id":118,"doc_module":4,"doc_module_name":25,"category_name":121,"show_sort_weight":118,"slug":122},"World Cup","world-cup",{"id":124,"doc_module":4,"doc_module_name":25,"category_name":125,"show_sort_weight":124,"slug":126},10,"Lifestyle","lifestyle",{"id":128,"doc_module":4,"doc_module_name":25,"category_name":129,"show_sort_weight":97,"slug":130},19,"General","general",{"code":4,"msg":82,"data":132},{"doc_id":79,"user_id":133,"nickname":42,"user_avatar":134,"doc_module":4,"category_id":107,"category_name":29,"doc_title":10,"doc_description":12,"doc_content":135,"file_id":136,"file_url":137,"file_type":138,"file_size":139,"view_count":55,"is_deleted":4,"is_public":22,"is_downloadable":22,"audit_status":22,"page_count":55,"language":140,"language_code":8,"site_id":7,"html_lang":8,"table_of_contents":141,"faqs":142,"seo_title":143,"seo_description":12,"update_tm":144,"read_time":145,"preview_page_count":4},687207022233,"https://ap-avatar.wpscdn.com/davatar_155a257f0dc6eb9ab79c44ca47cae57d","Investigational New Drugs (2025) 43:1211–1221 [https://doi.org/10.1007/s10637-025-01591-y](https://doi.org/10.1007/s10637-025-01591-y)  \nPhase 1 dose escalation trial of the selective adenosine A2B antagonist PBF-1129 in patients with metastatic non-small cell lung cancer  \nDwight H. Owen1,2 · Ruohan Wu1 · Lai Wei3 · Mikhail Dikov1 · Shankar Suman1,8 · Po‑Lan Su1,4 · Joseph Amann1 · Shuxiao Guan1 · Daniel Spakowicz1,2 · Catherine Schweitzer5 · Carly Pilcher5 · Michael B. Smith6 · Sarah Ferguson5 · Julio Castro Palomino7 · Santiago Figueroa Pérez7 · Erin M. Bertino1 · Peter G. Shields1,2 · Kai He1,2 ·  \nCarolyn J. Presley1 · Gregory A. Otterson1 · William E. Carson1,2 · David P. Carbone1,2  \nReceived: 22 July 2025 / Accepted: 17 October 2025 / Published online: 3 December 2025 © The Author(s) 2025  \nSummary  \nThe adenosinergic pathway represents a critical immunometabolic checkpoint within the tumor microenvironment of nonsmall cell lung cancer (NSCLC), contributing to immune suppression and therapeutic resistance. PBF-1129, an oral, selective A2B adenosine receptor (A2BAR) antagonist, was evaluated in a phase 1, open-label, dose-escalation trial (NCT03274479) in patients with advanced/metastatic NSCLC who had progressed on standard therapies. All patients had previously received chemotherapy and immune checkpoint blockade. Twenty-one patients received escalating doses (40–320 mg once daily), with no dose-limiting toxicities observed. The most frequently reported treatment related adverse events of any grade were lymphocytopenia (n = 8, 38.1%), vomiting (n = 8, 38.1%), anorexia (n = 6, 28.5%), and fatigue (n = 6, 28.5%) . PBF-1129 showed dose-proportional pharmacokinetics and maintained plasma concentrations above the 90% maximal inhibitory concentration (IC90) of A2BAR at 320 mg for 24 h, which was determined to be the recommended phase 2 dose (RP2D) . Best response was stable disease in 3 out of 21 patients including 2 of 6 treated at RP2D. Immunophenotyping revealed post-treatment reductions in programmed cell death protein 1 (PD-1) expression on CD8⁺ T cells, which correlated with improved survival. The reduction of PD-1 expression on CD4⁺ T cells and decreased myeloid-derived suppressor cells were also associated with better outcomes. These findings suggest PBF-1129 is safe and modulates the systemic immune parameters, warranting further evaluation in combination with immune checkpoint blockade.  \nKeywords Non-small cell lung cancer · Phase 1 clinical trial · Adenosine receptor · Immunotherapy  \n\n| Dwight H. Owen and Ruohan Wu contributed equally to this work. |\n| --- |\n| [ClinicalTrials.gov:NCT03274479](ClinicalTrials.gov:NCT03274479) |\n\n* Dwight H. Owen [Dwight.owen@osumc.edu](Dwight.owen@osumc.edu)  \n1 Division of Medical Oncology, Department of Internal Medicine, The Ohio State University Comprehensive Cancer Center, 1800 Cannon Drive, 12th Floor, Columbus, OH, USA  \n2 Pelotonia Institute for Immuno-Oncology, The Ohio State University Comprehensive Cancer Center, Columbus, OH, USA  \n3 Center for Biostatistics, The Ohio State University Wexner Medical Center, Columbus, OH, USA  \n4 Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Check Kung University, Tainan, Taiwan  \n5 Clinical Trials Office, The Ohio State University Comprehensive Cancer Center, Columbus, OH, USA  \n6 Department of Pharmacy, The Ohio State University Comprehensive Cancer Center, Columbus, OH, USA  \n7 Palobiofarma S.L., Pamplona, Spain  \n8 Department of Oncology, Mayo Clinic, Rochester, MN, USA  \nIntroduction  \nDespite recent progress in treating metastatic non-small cell lung cancer (mNSCLC), only a subset of tumors respond to currently available immunotherapy treatments; those that do respond eventually develop treatment resistance. A possible barrier to durable responses is the immunosuppressive tumor microenvironment (TME), which involves several immunosuppressive factors and cells. To develop a","cbCais3EtGa62O3i","https://ap.wps.com/l/cbCais3EtGa62O3i","pdf",1154500,"English","# Summary\n# Keywords\n# Introduction","[{\"question\":\"What does the study evaluate?\",\"answer\":\"The trial evaluates PBF-1129, an oral selective A2B adenosine receptor antagonist, in metastatic non-small cell lung cancer patients using a Phase 1 dose-escalation design.\"},{\"question\":\"How was dosing administered and what safety signal was observed?\",\"answer\":\"Patients received escalating once-daily doses of 40–320 mg. No dose-limiting toxicities were observed.\"},{\"question\":\"What biological and clinical responses were reported?\",\"answer\":\"Pharmacokinetics were dose-proportional with plasma concentrations above IC90 at 320 mg for 24 hours. Stable disease occurred in some patients, and post-treatment reductions in PD-1 expression on CD8+ T cells correlated with improved survival.\"}]","Phase 1 dose escalation trial of the selective adenosine A2B antagonist PBF-1129 in patients with metastatic non-small cell lung cancer | PDF",1790574179,28]