{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,27]],"date-time":"2026-10-27T06:31:23Z","timestamp":1793082683296,"version":"4.5.0"},"reference-count":23,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2016,10,11]],"date-time":"2016-10-11T00:00:00Z","timestamp":1476144000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"Lpath, Inc"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancer"],"published-print":{"date-parts":[[2017,2,15]]},"abstract":"<jats:sec>\n                    <jats:title>BACKGROUND<\/jats:title>\n                    <jats:p>Upregulation of sphingosine\u20101\u2010phosphate (S1P) may mediate resistance to vascular endothelial growth factor (VEGF)\u2010directed therapies and inhibit antitumor immunity. Antagonism of S1P in preclinical models appears to overcome this resistance. In this phase 2 study, the authors assessed the activity of sonepcizumab, a first\u2010in\u2010class inhibitor of S1P, in patients with metastatic renal cell carcinoma (mRCC) with a history of prior VEGF\u2010directed therapy.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS<\/jats:title>\n                    <jats:p>Patients were required to have clear cell mRCC and to have received treatment with at least 1 prior VEGF\u2010directed agent. Prior treatment with immunotherapeutic agents and \u22641 mammalian target of rapamycin inhibitors was permitted. The primary endpoint of the study was progression\u2010free survival. Additional endpoints included response rate and safety, and overall survival (OS) performed post hoc.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>\n                      A total of 40 patients were enrolled with a median of 3 prior therapies (range, 1\u20105 prior therapies), 78% of whom had intermediate\u2010risk disease by second\u2010line International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) criteria. Although the current study did not achieve its primary endpoint based on the 2\u2010month progression\u2010free survival, a median OS of 21.7 months was observed. Four patients (10%) demonstrated a partial response, with a median duration of response of 5.9 months. No grade 3\/4 treatment\u2010related adverse events were observed in &gt;5% of patients (adverse events were graded and recorded for each patient using Common Terminology Criteria for Adverse Events [version 4.0]); the most frequent grade 1\/2 treatment\u2010related adverse events were fatigue (30%), weight gain (18%), constipation (15%), and nausea (15%). Biomarker studies demonstrated an increase in S1P concentrations with therapy. Comprehensive genomic profiling of 3 patients with a clinical benefit of &gt;24 months indicated von Hippel\u2013Lindau (\n                      <jats:italic>VHL<\/jats:italic>\n                      ) and polybromo\u20101 (\n                      <jats:italic>PBRM1<\/jats:italic>\n                      ) alterations.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSIONS<\/jats:title>\n                    <jats:p>\n                      The encouraging OS and favorable safety profile observed with sonepcizumab should prompt further investigation of the agent in combination with VEGF\u2010directed agents or checkpoint inhibitors.\n                      <jats:bold>\n                        <jats:italic>Cancer<\/jats:italic>\n                        2017;123:576\u2013582.\n                      <\/jats:bold>\n                      \u00a9\n                      <jats:italic>2016 American Cancer Society<\/jats:italic>\n                      .\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/cncr.30393","type":"journal-article","created":{"date-parts":[[2016,10,13]],"date-time":"2016-10-13T12:19:50Z","timestamp":1476361190000},"page":"576-582","source":"Crossref","is-referenced-by-count":54,"title":["A phase 2 study of the sphingosine\u20101\u2010phosphate antibody sonepcizumab in patients with metastatic renal cell carcinoma"],"prefix":"10.1002","volume":"123","author":[{"given":"Sumanta K.","family":"Pal","sequence":"first","affiliation":[{"name":"Department of Medical Oncology and Experimental Therapeutics City of Hope Comprehensive Cancer Center Duarte California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Harry A.","family":"Drabkin","sequence":"additional","affiliation":[{"name":"Division of Hematology\/Oncology, Department of Medicine Medical University of South Carolina Charleston South Carolina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James A.","family":"Reeves","sequence":"additional","affiliation":[{"name":"Florida Cancer Specialists Fort Myers Florida"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John D.","family":"Hainsworth","sequence":"additional","affiliation":[{"name":"Sarah Cannon Research Institute Nashville Tennessee"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susan E.","family":"Hazel","sequence":"additional","affiliation":[{"name":"Lpath Inc San Diego California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dario A.","family":"Paggiarino","sequence":"additional","affiliation":[{"name":"Lpath Inc San Diego California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jon","family":"Wojciak","sequence":"additional","affiliation":[{"name":"Lpath Inc San Diego 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