{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,23]],"date-time":"2026-06-23T04:43:59Z","timestamp":1782189839923,"version":"3.54.5"},"reference-count":21,"publisher":"Springer Science and Business Media LLC","issue":"4","license":[{"start":{"date-parts":[[2024,7,22]],"date-time":"2024-07-22T00:00:00Z","timestamp":1721606400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2024,7,22]],"date-time":"2024-07-22T00:00:00Z","timestamp":1721606400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Invest New Drugs"],"published-print":{"date-parts":[[2024,8]]},"abstract":"<jats:sec>\n                <jats:title>Abstract<\/jats:title>\n                <jats:p>This phase 1b study aimed to evaluate the dose-limiting toxicity (DLT), maximum tolerated dose (MTD), pharmacokinetics, and preliminary efficacy of HR070803, a novel nanoliposomal formulation of irinotecan, in combination with 5-fluorouracil and leucovorin in patients with pretreated advanced solid tumors. This study consisted of dose-escalation and expansion stages. Dose escalation was performed with a traditional 3\u2009+\u20093 design; patients received intravenous infusion of HR070803 from 60 to 80 mg\/m<jats:sup>2<\/jats:sup>, followed by leucovorin (200 mg\/m<jats:sup>2<\/jats:sup>) and 5-fluorouracil (2000 mg\/m<jats:sup>2<\/jats:sup>) every 2 weeks. In the expansion stage, patients received treatments at selected tolerable dose. Fifteen patients received treatments at 60 mg\/m<jats:sup>2<\/jats:sup> (<jats:italic>n<\/jats:italic>\u2009=\u200912) and 80 mg\/m<jats:sup>2<\/jats:sup> (<jats:italic>n<\/jats:italic>\u2009=\u20093). DLTs occurred in 2 patients at 80 mg\/m<jats:sup>2<\/jats:sup> (grade 2 neutropenia that resulted in a dose delay of \u2265\u20097 days, <jats:italic>n<\/jats:italic>\u2009=\u20091; grade 3 febrile neutropenia, <jats:italic>n<\/jats:italic>\u2009=\u20091). The MTD was determined to be 60 mg\/m<jats:sup>2<\/jats:sup>. The most frequent HR070803related adverse events included anorexia, leukopenia, neutropenia, nausea, fatigue, and diarrhea. SN-38, the active metabolite of irinotecan, exhibited lower maximum plasma concentrations and a prolonged terminal half-life when irinotecan was administered via nanoliposome compared to conventional injection. Overall, 4 patients achieved a partial response (confirmed, <jats:italic>n<\/jats:italic>\u2009=\u20092), and 9 had stable disease. The MTD of HR070803 was 60 mg\/m<jats:sup>2<\/jats:sup> when infused with 5-fluorouracil and leucovorin. Nanoliposomal encapsulation modified the pharmacokinetics of irinotecan and SN-38. HR070803 with 5-fluorouracil and leucovorin demonstrated a manageable safety profile and promising antitumor efficacy in advanced solid tumors.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Trial registration<\/jats:title>\n                <jats:p>Clinicaltrials.gov, NCT05086848. Retrospectively registered on Oct. 12, 2021.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1007\/s10637-024-01442-2","type":"journal-article","created":{"date-parts":[[2024,7,22]],"date-time":"2024-07-22T11:06:30Z","timestamp":1721646390000},"page":"462-470","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Liposomal irinotecan (HR070803) in combination with 5-fluorouracil and leucovorin in patients with advanced solid tumors: a phase 1b dose-escalation and expansion study"],"prefix":"10.1007","volume":"42","author":[{"given":"Dongmei","family":"Ji","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weina","family":"Shen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ting","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huan","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianling","family":"Bai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junning","family":"Cao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xichun","family":"Hu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,7,22]]},"reference":[{"key":"1442_CR1","doi-asserted-by":"publisher","first-page":"104398","DOI":"10.1016\/j.phrs.2019.104398","volume":"148","author":"C Bailly","year":"2019","unstructured":"Bailly C (2019) Irinotecan: 25 years of cancer treatment. 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This trial conformed to the International Conference on Harmonization Good Clinical Practice guidelines and Good Clinical Laboratory Practice. The study was reported in accordance with ICMJE and Good Publication Practice Guidelines.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval"}},{"value":"Written informed consent forms were signed by all patients prior to initiating any studyrelated activities.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent to participate"}},{"value":"Not applicable.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent to publish"}},{"value":"Jianling Bai received research grant from Jiangsu Hengrui Pharmaceuticals Co., Ltd. Huan Wang was the employee of Jiangsu Hengrui Pharmaceuticals Co., Ltd. No potential conflicts of interest are reported from other authors.","order":5,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}]}}