{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T00:37:40Z","timestamp":1789519060413,"version":"build-2803163510"},"reference-count":25,"publisher":"American Society of Clinical Oncology (ASCO)","content-domain":{"domain":["ascopubs.org"],"crossmark-restriction":true},"short-container-title":["JCO"],"abstract":"<jats:sec>\n            <jats:title>PURPOSE<\/jats:title>\n            <jats:p>This early-phase study evaluated safety\/tolerability, pharmacokinetics, and preliminary efficacy of dendrimer-nanoparticle delivery platform (DEP)-SN38, a polylysine-based nanoparticle conjugate of the irinotecan active metabolite, SN38.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>METHODS<\/jats:title>\n            <jats:p>Adults with advanced solid tumors received DEP-SN38 intravenously once every 3 weeks (Q3W) or once every 2 weeks (Q2W) monotherapy, or Q2W combined with fluorouracil\/leucovorin (FU\/LV) to identify a recommended dose for each regimen. Primary end points were safety\/tolerability. Secondary end points included efficacy (RECIST-v1.1) and pharmacokinetics.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>RESULTS<\/jats:title>\n            <jats:p>\n              Heavily pretreated patients (N = 114; median 4 previous therapies) received DEP-SN38 (8-15-mg\/m\n              <jats:sup>2<\/jats:sup>\n              SN38), with 12.5 mg\/m\n              <jats:sup>2<\/jats:sup>\n              recommended for all regimens. Most DEP-SN38\u2013attributed treatment-related adverse events (TRAEs) were mild\/moderate (89.7%), with neutropenia the key dose-limiting toxicity and the most common grade 3\/4 TRAE (48% of grade 3\/4 events). Severe GI TRAEs were rare (grade 3 diarrhea and vomiting [0.9% of patients each]; nausea [1.8%]). Cholinergic symptoms were not observed. Efficacy signals were observed across several tumor types, particularly Q2W regimens and in patients with platinum-resistant ovarian cancer (PROC) and colorectal cancer (CRC). Among evaluable patients, objective response rates for Q3W or Q2W monotherapy and Q2W DEP-SN38\/FU\/LV were 1.8%, 21.4% (PROC 42.9%), and 12.5% (CRC 14.3%), respectively; disease control rates were 56.4%, 71.4%, and 81.3%, respectively. Median progression-free survival (PFS, all treated) was 2.1, 6.0, and 4.2 months for Q3W, Q2W, and Q2W DEP-SN38\/FU\/LV, respectively. Patients achieving PFS for at least 6 months included seven PROC (Q2W monotherapy, n = 5; &gt; 12 months, n = 3), 12 CRC (DEP-SN38\/FU\/LV, n = 6, including four patients for &gt;12 months), one pancreatic (10.2 months), one non-small cell lung (8.4 months), and two with breast cancer (16.6 months, 6 months).\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>CONCLUSION<\/jats:title>\n            <jats:p>DEP-SN38 was clinically well tolerated with minimal severe GI TRAEs. Preliminary antitumor activity in heavily pretreated patients with cancer demonstrates the potential clinical utility of DEP-SN38 monotherapy and combination regimens.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1200\/jco-25-00236","type":"journal-article","created":{"date-parts":[[2025,8,1]],"date-time":"2025-08-01T19:59:14Z","timestamp":1754078354000},"update-policy":"https:\/\/doi.org\/10.1200\/crossmark","source":"Crossref","is-referenced-by-count":2,"title":["Dendrimer-Nanoparticle (DEP) Delivery of Topoisomerase I Inhibitor, SN38 (DEP-SN38): Safety, Tolerability, and Preliminary Efficacy Study in Patients With Advanced Solid Tumors"],"prefix":"10.1200","clinical-trial-number":[{"clinical-trial-number":"isrctn99654100","registry":"10.18810\/isrctn"}],"author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4442-6516","authenticated-orcid":true,"given":"Jia","family":"Liu","sequence":"first","affiliation":[{"name":"The Kinghorn Cancer Centre, St Vincent's Hospital, Sydney, NSW, Australia"},{"name":"Faculty of Medicine and Health, School of Clinical Medicine, UNSW Sydney, Kensington, NSW, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9339-7101","authenticated-orcid":true,"given":"Anna R.","family":"Minchom","sequence":"additional","affiliation":[{"name":"The Royal Marsden Hospital NHS Foundation Trust, London, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9168-0387","authenticated-orcid":true,"given":"Alastair","family":"Greystoke","sequence":"additional","affiliation":[{"name":"Northern Centre for Cancer Care, Newcastle-Upon-Tyne Hospitals NHS Foundation Trust, Newcastle, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas R.J.","family":"Evans","sequence":"additional","affiliation":[{"name":"The Beatson West of Scotland Cancer Centre, University of Glasgow, Glasgow, United 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London, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wing","family":"Yau","sequence":"additional","affiliation":[{"name":"The Royal Marsden Hospital NHS Foundation Trust, London, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Burak Y.","family":"Aktas","sequence":"additional","affiliation":[{"name":"Guy's and St Thomas' NHS Foundation Trust and King's College, London, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rasha","family":"Cosman","sequence":"additional","affiliation":[{"name":"The Kinghorn Cancer Centre, St Vincent's Hospital, Sydney, NSW, Australia"},{"name":"Faculty of Medicine and Health, School of Clinical Medicine, UNSW Sydney, Kensington, NSW, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9400-5707","authenticated-orcid":true,"given":"Jordan E.","family":"Cohen","sequence":"additional","affiliation":[{"name":"The 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