{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T06:39:24Z","timestamp":1787812764200,"version":"build-2784847793"},"reference-count":31,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2019,2,23]],"date-time":"2019-02-23T00:00:00Z","timestamp":1550880000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"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":["Intl Journal of Cancer"],"published-print":{"date-parts":[[2019,10]]},"abstract":"<jats:p>PF\u201006647263, a novel antibody\u2013drug conjugate consisting of an anti\u2010EFNA4 antibody linked to a calicheamicin payload, has shown potent antitumor activity in human xenograft tumor models, including triple\u2010negative breast cancer (TNBC). In the dose\u2010escalation part 1 of this multicenter, open\u2010label, phase I study (NCT02078752), successive cohorts of patients (<jats:italic>n<\/jats:italic>, 48) with advanced solid tumors and no available standard therapy received PF\u201006647263 every 3 weeks (Q3W) or every week (QW), following a modified toxicity probability interval (mTPI) method (initial dosing: 0.015\u2009mg\/kg Q3W). Primary objective in part 1 was to estimate the maximum tolerated dose (MTD) and select the recommended phase 2 dose (RP2D). In part 2 (dose\u2010expansion cohort), 12 patients with pretreated, metastatic TNBC received PF\u201006647263 at the RP2D to further evaluate tumor response and overall safety. PF\u201006647263 QW administration (<jats:italic>n<\/jats:italic>, 23) was better tolerated than the Q3W regimen (<jats:italic>n<\/jats:italic>, 25) with only 1 DLT reported (thrombocytopenia). The most common AEs with the QW regimen (fatigue, nausea, vomiting, mucosal inflammation, thrombocytopenia, and diarrhea) were mostly mild to moderate in severity. The MTD was not estimated. PF\u201006647263 exposures increased in a dose\u2010related manner across the doses evaluated. The RP2D was determined to be 0.015\u2009mg\/kg QW. Six (10%) patients achieved a confirmed partial response and 22 (36.7%) patients had stable disease. No correlations were observed between tumor responses and <jats:italic>EFNA4<\/jats:italic> expression levels. Study findings showed manageable safety and favorable PK for PF\u201006647263 administered QW at the RP2D, with preliminary evidence of limited antitumor activity in patients with TNBC and ovarian cancer.<\/jats:p>","DOI":"10.1002\/ijc.32154","type":"journal-article","created":{"date-parts":[[2019,1,25]],"date-time":"2019-01-25T05:23:43Z","timestamp":1548393823000},"page":"1798-1808","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":43,"title":["First\u2010in\u2010human, phase I study of PF\u201006647263, an anti\u2010EFNA4 calicheamicin antibody\u2013drug conjugate, in patients with advanced solid tumors"],"prefix":"10.1002","volume":"145","author":[{"given":"Ignacio","family":"Garrido\u2010Laguna","sequence":"first","affiliation":[{"name":"Department of Medicine, Huntsman Cancer Institute, University of Utah Salt Lake City UT"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ian","family":"Krop","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Dana\u2010Farber Cancer Center\/Brigham and Women's Hospital  Boston MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"III","given":"Howard A.","family":"Burris","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Sarah Cannon Research Institute\/Tennessee Oncology  Nashville TN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erika","family":"Hamilton","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Sarah Cannon Research Institute\/Tennessee Oncology  Nashville TN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fadi","family":"Braiteh","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Comprehensive Cancer Centers of Nevada and University of Nevada Las Vegas School of Medicine  Las Vegas NV"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amy M.","family":"Weise","sequence":"additional","affiliation":[{"name":"Department of Oncology, Barbara Ann Karmanos Cancer Institute  Detroit MI"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maysa","family":"Abu\u2010Khalaf","sequence":"additional","affiliation":[{"name":"Department of Breast Medical Oncology, Thomas Jefferson University  Philadelphia PA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Theresa L.","family":"Werner","sequence":"additional","affiliation":[{"name":"Department of Medicine, Huntsman Cancer Institute, University of Utah Salt Lake City UT"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven","family":"Pirie\u2010Shepherd","sequence":"additional","affiliation":[{"name":"Pfizer Inc., Oncology  San Diego CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher J.","family":"Zopf","sequence":"additional","affiliation":[{"name":"Pfizer Inc., Oncology  San Diego CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mani","family":"Lakshminarayanan","sequence":"additional","affiliation":[{"name":"Pfizer Inc., Oncology  San Diego CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jaymes S.","family":"Holland","sequence":"additional","affiliation":[{"name":"Pfizer Inc., Oncology  San Diego CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raffaele","family":"Baffa","sequence":"additional","affiliation":[{"name":"Pfizer Inc., Oncology  San Diego CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8721-1609","authenticated-orcid":false,"given":"David S.","family":"Hong","sequence":"additional","affiliation":[{"name":"Department of Investigational Cancer Therapeutics, University of Texas M. 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