{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T15:10:58Z","timestamp":1793373058745,"version":"4.5.0"},"reference-count":16,"publisher":"Springer Science and Business Media LLC","issue":"5","license":[{"start":{"date-parts":[[2021,4,15]],"date-time":"2021-04-15T00:00:00Z","timestamp":1618444800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2021,4,15]],"date-time":"2021-04-15T00:00:00Z","timestamp":1618444800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100007156","name":"Innovation and Technology Commission - Hong Kong","doi-asserted-by":"publisher","award":["UIM 279"],"award-info":[{"award-number":["UIM 279"]}],"id":[{"id":"10.13039\/501100007156","id-type":"DOI","asserted-by":"publisher"}]},{"name":"BCT International Ltd","award":["N\/A"],"award-info":[{"award-number":["N\/A"]}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Invest New Drugs"],"published-print":{"date-parts":[[2021,10]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    <jats:italic>Background<\/jats:italic>\n                    : Pegylated recombinant human arginase (PEG-BCT-100) is an arginine depleting drug. Preclinical studies showed that HCC is reliant on exogenous arginine for growth due to the under-expression of the arginine regenerating enzymes argininosuccinate synthetase (ASS) and ornithine transcarbamylase (OTC).\n                    <jats:italic>Methods<\/jats:italic>\n                    : This is a single arm open-label Phase II trial to assess the potential clinical efficacy of PEG-BCT-100 in chemo na\u00efve sorafenib-failure HCC patients. Pre-treatment tumour biopsy was mandated for ASS and OTC expression by immunohistochemistry (IHC). Weekly intravenous PEG-BCT-100 at 2.7\u00a0mg\/kg was given. Primary endpoint was time to progression (TTP); secondary endpoints included radiological response as per RECIST1.1, progression free survival (PFS) and overall survival (OS). Treatment outcomes were correlated with tumour immunohistochemical expressions of ASS and OTC.\n                    <jats:italic>Results<\/jats:italic>\n                    : In total 27 patients were recruited. The median TTP and PFS were both 6\u00a0weeks (95% CI, 5.9\u20136.0\u00a0weeks). The disease control rate (DCR) was 21.7% (5 stable disease). The drug was well tolerated. Post hoc analysis showed that duration of arginine depletion correlated with OS. For patients with available IHC results, 10 patients with ASS-negative tumour had OS of 35\u00a0weeks (95% CI: 8.3\u201378.0\u00a0weeks) vs. 15.14\u00a0weeks (95% CI: 13.4\u201315.1\u00a0weeks) in 3 with ASS-positive tumour; expression of OTC did not correlate with treatment outcomes.\n                    <jats:italic>Conclusions<\/jats:italic>\n                    : PEG-BCT-100 in chemo na\u00efve post-sorafenib HCC is well tolerated with moderate DCR. ASS-negative confers OS advantage over ASS-positive HCC. ASS-negativity is a potential biomarker for OS in HCC and possibly for other ASS-negative arginine auxotrophic cancers. Trial registration number: NCT01092091. Date of registration: March 23, 2010.\n                  <\/jats:p>","DOI":"10.1007\/s10637-021-01111-8","type":"journal-article","created":{"date-parts":[[2021,4,15]],"date-time":"2021-04-15T10:38:42Z","timestamp":1618483122000},"page":"1375-1382","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":47,"title":["A phase II clinical study on the efficacy and predictive biomarker of pegylated recombinant arginase on hepatocellular carcinoma"],"prefix":"10.1007","volume":"39","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8998-5480","authenticated-orcid":false,"given":"Stephen L.","family":"Chan","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul N.M.","family":"Cheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angela M.","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Landon L.","family":"Chan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leung","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cheuk M.","family":"Chu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charing C.N.","family":"Chong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yat M.","family":"Lau","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Winnie","family":"Yeo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kelvin K.C.","family":"Ng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simon C.H.","family":"Yu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tony S.K.","family":"Mok","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anthony W.H.","family":"Chan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,4,15]]},"reference":[{"key":"1111_CR1","doi-asserted-by":"publisher","first-page":"87","DOI":"10.1146\/annurev.nutr.22.110801.140547","volume":"22","author":"SM Morris Jr","year":"2002","unstructured":"Morris SM Jr (2002) Regulation of enzymes of the urea cycle and arginine metabolism. 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Chan has served as an advisory committee member for MSD, Astra-Zeneca, Eisai and Ipsen. None for other authors.","order":5,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflicts of interest\/competing interests"}}]}}