{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T03:27:32Z","timestamp":1791430052045,"version":"4.3.3"},"reference-count":15,"publisher":"Oxford University Press (OUP)","issue":"11","license":[{"start":{"date-parts":[[2021,9,22]],"date-time":"2021-09-22T00:00:00Z","timestamp":1632268800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,11,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Lessons Learned<\/jats:title>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>We conducted a first-in-human, first-in-class, phase I study of SGN-2FF, a potent small-molecule inhibitor of glycoprotein fucosylation, in patients with advanced solid tumors.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>The study consisted of four parts: SGN-2FF monotherapy dose-escalation (part A) and expansion (part B), and SGN-2FF\u00a0+\u00a0pembrolizumab dose-escalation (part C) and expansion (part D). The objectives were to evaluate safety and tolerability, maximum tolerated dose (MTD), pharmacokinetics (PK), pharmacodynamics (PD), and antitumor activity of SGN-2FF monotherapy and SGN-2FF + pembrolizumab.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Forty-six patients were enrolled (part A, n\u00a0=\u200933; part B, n\u00a0=\u20096; part C, n\u00a0=\u20097; part D did not enroll any patients). During part A (n\u00a0=\u200932) exploring 1\u201315 g once daily (QD) and 2\u20135 g twice daily (b.i.d.), grade 3 dose-limiting toxicities were diarrhea (2 g and 15 g QD) and increased lipase (2 g QD). The MTD was 10 g daily. In part A, common toxicities were grades 1\u20132 diarrhea, fatigue, and nausea (each 47%); thromboembolic events (grades 2\u20135) occurred in 5 of 32 patients (16%). Safety measures included concurrent prophylactic anticoagulation with low-molecular weight heparin (LMWH). In part C, despite the safety measures implemented, a thromboembolic event occurred in one of seven patients (14%) during the SGN-2FF lead-in period. Of 28 evaluable patients in part A, 1 patient with advanced head and neck squamous cell carcinoma achieved Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 complete response (CR) and 10 (36%) had RECIST v1.1 stable disease, including 1 patient with advanced triple-negative breast cancer with 51% tumor burden reduction. SGN-2FF administration led to dose-proportional increases in exposure and PD reduction in protein fucosylation.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>SGN-2FF demonstrated proof-of-mechanism and preliminary antitumor activity but was associated with thromboembolic events leading to study termination.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1002\/onco.13911","type":"journal-article","created":{"date-parts":[[2021,7,20]],"date-time":"2021-07-20T12:26:08Z","timestamp":1626783968000},"page":"925-e1918","source":"Crossref","is-referenced-by-count":44,"title":["<scp>First-In-Human<\/scp>, <scp>First-In-Class<\/scp>, Phase I Trial of the Fucosylation Inhibitor <scp>SGN-2FF<\/scp> in Patients with Advanced Solid Tumors"],"prefix":"10.1093","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9411-8899","authenticated-orcid":false,"given":"Khanh T.","family":"Do","sequence":"first","affiliation":[{"name":"Dana-Farber Cancer Institute, Boston, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura Quan Man","family":"Chow","sequence":"additional","affiliation":[{"name":"University of Washington, Seattle Cancer Care Alliance, Seattle, Washington, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karen","family":"Reckamp","sequence":"additional","affiliation":[{"name":"City of Hope Comprehensive Cancer Center, Duarte, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rachel E.","family":"Sanborn","sequence":"additional","affiliation":[{"name":"Earle A. Chiles Research Institute, Providence Cancer Institute, Portland, Oregon, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Howard","family":"Burris","sequence":"additional","affiliation":[{"name":"Sarah Cannon Research Institute, Nashville, Tennessee, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francisco","family":"Robert","sequence":"additional","affiliation":[{"name":"University of Alabama at Birmingham, Birmingham, Alabama, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D. 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