{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,18]],"date-time":"2025-10-18T21:02:59Z","timestamp":1760821379376,"version":"build-2065373602"},"reference-count":28,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2023,3,7]],"date-time":"2023-03-07T00:00:00Z","timestamp":1678147200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["acsjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer"],"published-print":{"date-parts":[[2023,5,15]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>The nucleoside FF\u201010502\u201001, structurally similar to but with different biologic effects than gemcitabine, shows promising activity both alone and combined with cisplatin in preclinical gemcitabine\u2010resistant tumor models. We conducted an open\u2010label, single\u2010arm, 3\u00a0+\u00a03 first\u2010in\u2010human trial to explore the safety, tolerability, and antitumor activity of FF\u201010502\u201001 in patients with solid tumors.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Patients with inoperable metastatic tumors refractory to standard therapies were enrolled. Escalating intravenous FF\u201010502\u201001 doses (8\u2013135\u00a0mg\/m<jats:sup>2<\/jats:sup>) were administered weekly for 3\u00a0weeks in 28\u2010day cycles until progressive disease or unacceptable toxicity was observed. Three expansion cohorts were subsequently evaluated.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>A phase 2 dose of 90\u00a0mg\/m<jats:sup>2<\/jats:sup> was determined after evaluating 40 patients. Dose\u2010limiting toxicities included hypotension and nausea. Phase 2a enrolled patients with cholangiocarcinoma (36), gallbladder cancer (10), and pancreatic\/other tumors (20). Common adverse events were grade 1\u20132 rash, pruritus, fever, and fatigue. Grade 3 or 4 hematologic toxicities were observed at low incidences, including thrombocytopenia (5.1%) and neutropenia (2%). Confirmed partial responses (PRs) occurred in five patients with gemcitabine\u2010refractory tumors, including three with cholangiocarcinoma and one each with gallbladder and urothelial cancer. Median progression\u2010free and overall survival rates in patients with\u00a0cholangiocarcinoma were 24.7 and 39.1\u00a0weeks, respectively. Prolonged progression\u2010free survival in patients with cholangiocarcinoma was associated with <jats:italic>BAP1<\/jats:italic> and <jats:italic>PBRM1<\/jats:italic> mutations.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>FF\u201010502\u201001 was well tolerated with manageable side effects and limited hematologic toxicity. Durable PRs and disease stabilizations were observed in heavily pretreated biliary tract patients who had received prior gemcitabine. FF\u201010502\u201001 is distinct from gemcitabine and may represent an effective therapy.<\/jats:p><\/jats:sec>","DOI":"10.1002\/cncr.34709","type":"journal-article","created":{"date-parts":[[2023,3,7]],"date-time":"2023-03-07T22:26:10Z","timestamp":1678227970000},"page":"1537-1546","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["A phase 1\/2a safety, pharmacokinetics, and efficacy study of the novel nucleoside analog FF\u201010502\u201001 for the treatment of advanced solid tumors"],"prefix":"10.1002","volume":"129","author":[{"given":"Filip","family":"Janku","sequence":"first","affiliation":[{"name":"Department of Investigational Cancer Therapeutics The University of Texas MD Anderson Cancer Center  Houston Texas USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9158-0941","authenticated-orcid":false,"given":"Milind M.","family":"Javle","sequence":"additional","affiliation":[{"name":"Department of Gastrointestinal Medical Oncology The University of Texas MD Anderson Cancer Center  Houston Texas USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shiraj","family":"Sen","sequence":"additional","affiliation":[{"name":"Sarah Cannon Research Institute at HealthONE  Denver Colorado USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9281-480X","authenticated-orcid":false,"given":"Shubham","family":"Pant","sequence":"additional","affiliation":[{"name":"Department of Gastrointestinal Medical Oncology The University of Texas MD Anderson Cancer Center  Houston Texas USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lindsay G.","family":"Bramwell","sequence":"additional","affiliation":[{"name":"Sarah Cannon Research Institute at HealthONE  Denver Colorado USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6064-6837","authenticated-orcid":false,"given":"Vivek","family":"Subbiah","sequence":"additional","affiliation":[{"name":"Department of Investigational Cancer Therapeutics The University of Texas MD Anderson Cancer Center  Houston Texas USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tracey","family":"Way","sequence":"additional","affiliation":[{"name":"Sarah Cannon Research Institute at HealthONE  Denver Colorado USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David S.","family":"Wages","sequence":"additional","affiliation":[{"name":"FUJIFILM Pharmaceuticals U.S.A., Inc.  Cambridge Massachusetts USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Catherine A.","family":"Wheeler","sequence":"additional","affiliation":[{"name":"FUJIFILM Pharmaceuticals U.S.A., Inc.  Cambridge Massachusetts USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Takeaki","family":"Suzuki","sequence":"additional","affiliation":[{"name":"FUJIFILM Pharmaceuticals U.S.A., Inc.  Cambridge Massachusetts USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kazunori","family":"Saeki","sequence":"additional","affiliation":[{"name":"FUJIFILM Corporation  Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ruth Ann","family":"Subach","sequence":"additional","affiliation":[{"name":"FUJIFILM Pharmaceuticals U.S.A., Inc.  Cambridge Massachusetts USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Timothy","family":"Madden","sequence":"additional","affiliation":[{"name":"FUJIFILM Pharmaceuticals U.S.A., Inc.  Cambridge Massachusetts USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gary","family":"Maier","sequence":"additional","affiliation":[{"name":"FUJIFILM Pharmaceuticals U.S.A., Inc.  Cambridge Massachusetts USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0118-2224","authenticated-orcid":false,"given":"Mary J.","family":"Johansen","sequence":"additional","affiliation":[{"name":"FUJIFILM Pharmaceuticals U.S.A., Inc.  Cambridge Massachusetts USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kin","family":"Cheung","sequence":"additional","affiliation":[{"name":"FUJIFILM Pharmaceuticals U.S.A., Inc.  Cambridge Massachusetts USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gerald S.","family":"Falchook","sequence":"additional","affiliation":[{"name":"Sarah Cannon Research Institute at HealthONE  Denver Colorado USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2023,3,7]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1200\/jco.1991.9.3.491"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.118.248740"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/s0304\u20103835(99)00221\u20109"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1158\/1538\u20107445.AM2018\u2010326"},{"volume-title":"Phase I cancer clinical trials: a practical guide","year":"2006","author":"Eisenhauer EA","key":"e_1_2_9_6_1"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejca.2008.10.026"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1021\/ac100984h"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2012.43.8150"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10072\u2010011\u20100494\u20107"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.5707"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa0908721"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00280\u2010013\u20102090\u20104"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/s1470\u20102045(21)00341\u20107"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10637\u2010018\u20100670\u20101"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1093\/annonc\/mdu162"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejca.2012.08.003"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/bjc.2017.119"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1007\/bf00873232"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/bjc.1996.18"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.3390\/cancers12082039"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11864\u2010020\u201000767\u20103"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ctrv.2018.09.002"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/s1470\u20102045(20)30321\u20101"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.21037\/jgo.2017.03.06"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.32463"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ctrv.2020.102091"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrd.2016.256"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1158\/2159\u20108290.Cd\u201016\u20100860"}],"container-title":["Cancer"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cncr.34709","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/cncr.34709","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/acsjournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cncr.34709","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,12]],"date-time":"2025-10-12T19:43:37Z","timestamp":1760298217000},"score":1,"resource":{"primary":{"URL":"https:\/\/acsjournals.onlinelibrary.wiley.com\/doi\/10.1002\/cncr.34709"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,3,7]]},"references-count":28,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2023,5,15]]}},"alternative-id":["10.1002\/cncr.34709"],"URL":"https:\/\/doi.org\/10.1002\/cncr.34709","archive":["Portico"],"relation":{},"ISSN":["0008-543X","1097-0142"],"issn-type":[{"type":"print","value":"0008-543X"},{"type":"electronic","value":"1097-0142"}],"subject":[],"published":{"date-parts":[[2023,3,7]]},"assertion":[{"value":"2022-10-28","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-12-21","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-03-07","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}