{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,2]],"date-time":"2026-11-02T22:52:38Z","timestamp":1793659958578,"version":"4.5.1"},"reference-count":24,"publisher":"BMJ","issue":"1","license":[{"start":{"date-parts":[[2026,2,17]],"date-time":"2026-02-17T00:00:00Z","timestamp":1771286400000},"content-version":"unspecified","delay-in-days":47,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100013226","name":"Les Laboratories Pierre Fabre","doi-asserted-by":"publisher","award":["N\/A"],"award-info":[{"award-number":["N\/A"]}],"id":[{"id":"10.13039\/100013226","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["bmjonc"],"accepted":{"date-parts":[[2026,1,20]]},"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>W0180 is a humanised IgG1\u03ba antagonistic monoclonal antibody against the V domain-containing immunoglobulin suppressor of T-cell activation (VISTA) designed to enhance antitumour activities by inhibiting the immunosuppressive role of VISTA in myeloid cells and T cells in solid tumours.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and analysis<\/jats:title>\n                    <jats:p>Preclinical experiments evaluated the pharmacodynamics and antitumour activity of W0180. A first-in-human phase 1 dose-escalation study investigated the maximum tolerated dose (MTD), safety\/tolerability, preliminary efficacy, pharmacokinetics and pharmacodynamics of W0180, both as monotherapy and in combination with pembrolizumab (an anti-programmed cell death protein-1 (PD-1) therapy), with the aim of establishing a recommended dose for expansion (RDE). In the monotherapy arm, cohorts of patients with locally advanced\/metastatic solid tumours received once-weekly W0180 at increasing doses (from 3.5 to 600\u2009mg). In the combination therapy arm, patients with relapsed\/refractory, advanced\/metastatic solid tumours and \u22651 prior anti-PD (ligand)-1 therapy line received W0180 (60 or 300\u2009mg)+pembrolizumab.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>W0180 exhibited pH-independent blockade of the VISTA-ligand interaction in vitro and showed antitumour activity in a syngeneic preclinical murine model expressing human VISTA. In the phase 1 study, of the 33 patients in the monotherapy (n=24) or combination therapy (n=9) arms, 28 contributed to dose determination. Dose-limiting toxicities were Grade 2 cerebral infarction and Grade 3 infusion-related reaction (IRR; n=1\u2009each). The study was terminated prematurely in the dose-escalation phase (due to a business decision by the sponsor) before the MTD\/RDE was reached. Common related treatment-emergent adverse events were IRR and fatigue; most were of mild severity. No patients achieved Response Evaluation Criteria in Solid Tumours objective response; two had prolonged stable disease (SD; one from each arm). Biomarker analysis suggested a dose-dependent pharmacodynamic effect of W0180.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>W0180 demonstrated manageable safety, preliminary signs of clinical activity with prolonged SD and dose-dependent pharmacodynamics consistent with preclinical data (even though MTD was not reached) in patients with locally advanced\/metastatic tumours, both as monotherapy and in combination with anti-programmed cell death protein-1 therapy.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Trial registration number<\/jats:title>\n                    <jats:p>\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"clintrialgov\" specific-use=\"clinicaltrial \" xlink:href=\"NCT04564417\">NCT04564417<\/jats:ext-link>\n                      .\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/bmjonc-2025-000854","type":"journal-article","created":{"date-parts":[[2026,3,4]],"date-time":"2026-03-04T18:11:59Z","timestamp":1772647919000},"page":"e000854","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":3,"title":["First-in-human phase 1 dose-escalation study of W0180, an anti-VISTA monoclonal antibody, with and without pembrolizumab in patients with locally advanced or metastatic solid tumours"],"prefix":"10.1136","volume":"5","clinical-trial-number":[{"clinical-trial-number":"nct04564417","registry":"10.18810\/clinical-trials-gov"},{"clinical-trial-number":"nct04564417","registry":"10.18810\/clinical-trials-gov"}],"author":[{"given":"Carlos","family":"Gomez-Roca","sequence":"first","affiliation":[{"name":"Department of Medical Oncology & Clinical Research Unit, Oncopole Claudius Regaud, IUCT-Oncopole, University of Toulouse, Toulouse, 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