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A phase I study of the human anti-activin receptor-like kinase 1 antibody PF-03446962 in Asian patients with advanced solid tumors
DC Field | Value | Language |
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dc.contributor.author | Doi, Toshihiko | - |
dc.contributor.author | Lee, Kyung-Hun | - |
dc.contributor.author | Kim, Tae-Min | - |
dc.contributor.author | Ohtsu, Atsushi | - |
dc.contributor.author | Kim, Tae Yong | - |
dc.contributor.author | Ikeda, Masafumi | - |
dc.contributor.author | Yoh, Kiyotaka | - |
dc.contributor.author | Stampino, Corrado Gallo | - |
dc.contributor.author | Hirohashi, Tomoko | - |
dc.contributor.author | Suzuki, Akiyuki | - |
dc.contributor.author | Fujii, Yosuke | - |
dc.contributor.author | Williams, James Andrew | - |
dc.contributor.author | Bang, Yung-Jue | - |
dc.date.accessioned | 2021-01-31T11:06:30Z | - |
dc.date.available | 2021-01-31T11:06:30Z | - |
dc.date.created | 2018-09-03 | - |
dc.date.issued | 2016-07 | - |
dc.identifier.citation | Cancer Medicine, Vol.5 No.7, pp.1454-1463 | - |
dc.identifier.issn | 2045-7634 | - |
dc.identifier.other | 49946 | - |
dc.identifier.uri | https://hdl.handle.net/10371/173028 | - |
dc.description.abstract | Preclinical studies suggest that ALK-1 signaling mediates a complementary angiogenesis pathway activated upon development of resistance to vascular endothelial growth factor (VEGF)-targeted therapies. Inhibition of ALK-1 signaling may lead to disruption of tumor angiogenesis and growth. We report findings from a multicenter, open-label, phase I study of the fully human anti-ALK-1 mAb PF-03446962 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 + 3 design (n = 16). In Part 2, patients were treated with PF-03446962 at 7 and 10 mg/kg (10/cohort), including patients with disease progression following prior VEGF receptor (R)-targeted therapy. Primary objectives were determination of the maximum tolerated dose (MTD) and recommended phase II dose (RP2D). Secondary objectives included safety, pharmacokinetics, pharmacodynamics, and antitumor activity of PF-03446962. No dose-limiting toxicity (DLT) was noted in the 12 DLT-evaluable patients. Treatment was well tolerated. The MTD for biweekly intravenous administration was estimated to be 10 mg/kg and the RP2D 7 mg/kg. Treatment\-related grades 1-3 thrombocytopenia was experienced by 27.8% patients. The most frequent nonhematologic treatment-related AEs were grades 1-2 pyrexia and epistaxis. Four patients (3/4 with hepatocellular carcinoma) developed telangiectasia suggesting vascular targeting and in vivo ALK-1 inhibition by PF-03446962. Stable disease for 12 weeks or more was observed in 25.7% of patients and in 44.4% of those with hepatocellular carcinoma. ALK-1 inhibition by PF-03446962 may represent a novel antiangiogenic strategy for patients with advanced solid malignancies complementary to current treatment with VEGF(R)-targeted inhibitors or chemotherapy. | - |
dc.language | 영어 | - |
dc.publisher | John Wiley and Sons Ltd | - |
dc.title | A phase I study of the human anti-activin receptor-like kinase 1 antibody PF-03446962 in Asian patients with advanced solid tumors | - |
dc.type | Article | - |
dc.contributor.AlternativeAuthor | 방영주 | - |
dc.identifier.doi | 10.1002/cam4.724 | - |
dc.citation.journaltitle | Cancer Medicine | - |
dc.identifier.wosid | 000380048900011 | - |
dc.identifier.scopusid | 2-s2.0-85006223109 | - |
dc.citation.endpage | 1463 | - |
dc.citation.number | 7 | - |
dc.citation.startpage | 1454 | - |
dc.citation.volume | 5 | - |
dc.identifier.sci | 000380048900011 | - |
dc.description.isOpenAccess | Y | - |
dc.contributor.affiliatedAuthor | Bang, Yung-Jue | - |
dc.type.docType | Article | - |
dc.description.journalClass | 1 | - |
dc.subject.keywordPlus | HEREDITARY HEMORRHAGIC TELANGIECTASIA | - |
dc.subject.keywordPlus | MONOCLONAL-ANTIBODY | - |
dc.subject.keywordPlus | ADVANCED CANCER | - |
dc.subject.keywordPlus | GROWTH-FACTOR | - |
dc.subject.keywordPlus | OPEN-LABEL | - |
dc.subject.keywordPlus | ALK1 | - |
dc.subject.keywordPlus | ENDOGLIN | - |
dc.subject.keywordPlus | TARGET | - |
dc.subject.keywordPlus | PHARMACOKINETICS | - |
dc.subject.keywordPlus | DALANTERCEPT | - |
dc.subject.keywordAuthor | Activin receptor-like kinase 1 | - |
dc.subject.keywordAuthor | bone morphogenetic protein | - |
dc.subject.keywordAuthor | hepatocellular carcinoma | - |
dc.subject.keywordAuthor | PF-03446962 | - |
dc.subject.keywordAuthor | solid tumors | - |
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