{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,8]],"date-time":"2026-06-08T20:37:24Z","timestamp":1780951044876,"version":"3.54.1"},"reference-count":28,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2024,12,30]],"date-time":"2024-12-30T00:00:00Z","timestamp":1735516800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2023YFE0204000"],"award-info":[{"award-number":["2023YFE0204000"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81972471"],"award-info":[{"award-number":["81972471"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82273204"],"award-info":[{"award-number":["82273204"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012245","name":"Science and Technology Planning Project of Guangdong Province","doi-asserted-by":"publisher","award":["2023B1212060013"],"award-info":[{"award-number":["2023B1212060013"]}],"id":[{"id":"10.13039\/501100012245","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100021171","name":"Basic and Applied Basic Research Foundation of Guangdong Province","doi-asserted-by":"publisher","award":["2023A1515012412"],"award-info":[{"award-number":["2023A1515012412"]}],"id":[{"id":"10.13039\/501100021171","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer Medicine"],"published-print":{"date-parts":[[2025,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aim<\/jats:title>\n                    <jats:p>This study aimed to determine the maximum tolerated dose (MTD) of the urokinase plasminogen activator (uPA) inhibitor upamostat (LH011) in combination with gemcitabine for locally advanced unresectable or metastatic pancreatic cancer.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Method<\/jats:title>\n                    <jats:p>\n                      Seventeen patients were enrolled and received escalating doses of oral LH011 (100, 200, 400, or 600\u2009mg) daily alongside 1000\u2009mg\/m\n                      <jats:sup>2<\/jats:sup>\n                      of gemcitabine. Safety profiles, tumor response (including response rate and progression\u2010free survival), pharmacokinetics, and changes in CA199 and D\u2010dimer levels were assessed.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>During the study period (Day0\u2013Day49), no patients achieved partial response. Stable disease (SD) was observed in 12 patients (70.6%), while four patients (23.5%) experienced progressive disease (PD). One patient withdrew due to a serious adverse event (SAE) on D47. Pharmacokinetic analysis revealed a dose\u2010related increase in LH011 and its metabolite WX\u2010UK1 exposure from 100 to 400\u2009mg but not in the 600\u2009mg group. Hematological toxicity, mainly attributable to gemcitabine, was the predominant grade 3 or 4 adverse event, with additional occurrences of loss of appetite, rash, and interstitial lung disease. Sinus bradycardia possibly linked to LH011 rather than gemcitabine was noted. The MTD was not reached.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Combining LH011 at doses ranging from 100 to 600\u2009mg with gemcitabine every 21\u2009days demonstrated manageable safety and tolerability. However, tumor response did not significantly differ among the dose groups, suggesting the need for further investigation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Trial Registration<\/jats:title>\n                    <jats:p>NCT05329597<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/cam4.70550","type":"journal-article","created":{"date-parts":[[2024,12,30]],"date-time":"2024-12-30T06:34:13Z","timestamp":1735540453000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Phase I Trial of Upamostat Combined With Gemcitabine in Locally Unresectable or Metastatic Pancreatic Cancer: Safety and Preliminary Efficacy Assessment"],"prefix":"10.1002","volume":"14","author":[{"given":"Xiuping","family":"Lai","sequence":"first","affiliation":[{"name":"Phase I Clinical Trial Center Sun Yat\u2010sen Memorial Hospital, Sun Yat\u2010sen University  Guangzhou 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