{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T02:41:41Z","timestamp":1790649701823,"version":"4.1.0"},"reference-count":24,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2016,4,14]],"date-time":"2016-04-14T00:00:00Z","timestamp":1460592000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100004319","name":"Pfizer","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004319","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer Medicine"],"published-print":{"date-parts":[[2016,7]]},"abstract":"Abstract<\/jats:title>Preclinical studies suggest that ALK<\/jats:styled-content>\u20101 signaling mediates a complementary angiogenesis pathway activated upon development of resistance to vascular endothelial growth factor (VEGF<\/jats:styled-content>)\u2010targeted therapies. Inhibition of ALK<\/jats:styled-content>\u20101 signaling may lead to disruption of tumor angiogenesis and growth. We report findings from a multicenter, open\u2010label, phase I study of the fully human anti\u2010ALK<\/jats:styled-content>\u20101 mA<\/jats:styled-content>b PF<\/jats:styled-content>\u201003446962 conducted in Japan and South Korea, in Asian patients with advanced solid tumors. The dose escalation Part 1 of the study was based on a standard 3\u00a0+\u00a03 design (n<\/jats:italic>\u00a0=\u00a016). In Part 2, patients were treated with PF<\/jats:styled-content>\u201003446962 at 7 and 10\u00a0mg\/kg (10\/cohort), including patients with disease progression following prior VEGF<\/jats:styled-content> receptor (R)\u2010targeted therapy. Primary objectives were determination of the maximum tolerated dose (MTD<\/jats:styled-content>) and recommended phase II<\/jats:styled-content> dose (RP<\/jats:styled-content>2D). Secondary objectives included safety, pharmacokinetics, pharmacodynamics, and antitumor activity of PF<\/jats:styled-content>\u201003446962. No dose\u2010limiting toxicity (DLT<\/jats:styled-content>) was noted in the 12 DLT<\/jats:styled-content>\u2010evaluable patients. Treatment was well tolerated. The MTD<\/jats:styled-content> for biweekly intravenous administration was estimated to be 10\u00a0mg\/kg and the RP<\/jats:styled-content>2D 7\u00a0mg\/kg. Treatment\u2010related grades 1\u20133 thrombocytopenia was experienced by 27.8% patients. The most frequent nonhematologic treatment\u2010related AE<\/jats:styled-content>s were grades 1\u20132 pyrexia and epistaxis. Four patients (3\/4 with hepatocellular carcinoma) developed telangiectasia suggesting vascular targeting and in vivo ALK<\/jats:styled-content>\u20101 inhibition by PF<\/jats:styled-content>\u201003446962. Stable disease for 12\u00a0weeks or more was observed in 25.7% of patients and in 44.4% of those with hepatocellular carcinoma. ALK<\/jats:styled-content>\u20101 inhibition by PF<\/jats:styled-content>\u201003446962 may represent a novel antiangiogenic strategy for patients with advanced solid malignancies complementary to current treatment with VEGF<\/jats:styled-content>(R)\u2010targeted inhibitors or chemotherapy.<\/jats:p>","DOI":"10.1002\/cam4.724","type":"journal-article","created":{"date-parts":[[2016,4,14]],"date-time":"2016-04-14T06:09:20Z","timestamp":1460614160000},"page":"1454-1463","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["A phase I study of the human anti\u2010activin receptor\u2010like kinase 1 antibody PF<\/scp>\u201003446962 in Asian patients with advanced solid tumors"],"prefix":"10.1002","volume":"5","author":[{"given":"Toshihiko","family":"Doi","sequence":"first","affiliation":[{"name":"National Cancer Center Hospital East 6\u20105\u20101 Kashiwanoha Kashiwa Chiba Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kyung\u2010Hun","family":"Lee","sequence":"additional","affiliation":[{"name":"Seoul National University College of Medicine and Hospital 101 Daehak\u2010ro Jongno\u2010gu Seoul 110\u2010744 South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tae\u2010Min","family":"Kim","sequence":"additional","affiliation":[{"name":"Seoul National University College of Medicine and Hospital 101 Daehak\u2010ro Jongno\u2010gu Seoul 110\u2010744 South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Atsushi","family":"Ohtsu","sequence":"additional","affiliation":[{"name":"National Cancer Center Hospital East 6\u20105\u20101 Kashiwanoha Kashiwa Chiba Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tae Yong","family":"Kim","sequence":"additional","affiliation":[{"name":"Seoul National University College of Medicine and Hospital 101 Daehak\u2010ro Jongno\u2010gu Seoul 110\u2010744 South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masafumi","family":"Ikeda","sequence":"additional","affiliation":[{"name":"National Cancer Center Hospital East 6\u20105\u20101 Kashiwanoha Kashiwa Chiba Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kiyotaka","family":"Yoh","sequence":"additional","affiliation":[{"name":"National Cancer Center Hospital East 6\u20105\u20101 Kashiwanoha Kashiwa Chiba Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Corrado","family":"Gallo Stampino","sequence":"additional","affiliation":[{"name":"Pfizer Global Oncology Research and Development Via Anna Maria Mozzoni, 12 Milan 20152 Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomoko","family":"Hirohashi","sequence":"additional","affiliation":[{"name":"Pfizer Japan 3\u201022\u20107 Yoyogi Shibuya\u2010ku Tokyo 151\u20108589 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