{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T21:08:11Z","timestamp":1792789691540,"version":"4.5.0"},"reference-count":36,"publisher":"BMJ","issue":"3","license":[{"start":{"date-parts":[[2026,3,13]],"date-time":"2026-03-13T00:00:00Z","timestamp":1773360000000},"content-version":"unspecified","delay-in-days":12,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100018688","name":"Symphogen","doi-asserted-by":"publisher","award":["N\/A"],"award-info":[{"award-number":["N\/A"]}],"id":[{"id":"10.13039\/501100018688","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100011725","name":"Servier","doi-asserted-by":"publisher","award":["N\/A"],"award-info":[{"award-number":["N\/A"]}],"id":[{"id":"10.13039\/501100011725","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["J Immunother Cancer"],"accepted":{"date-parts":[[2026,2,9]]},"published-print":{"date-parts":[[2026,3]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>T-cell immunoglobulin and mucin-domain containing 3 (TIM-3) is an inhibitory receptor linked to decreased antitumor activity of immune cells. S095018 is a human anti-TIM-3 IgG2 antibody that blocks the binding of phosphatidyl serine to TIM-3. Sym021 is a humanized IgG1 antibody that inhibits the binding of programmed cell death protein-1 (PD-1) to its ligands programmed death-ligand 1 (PD-L1) and PD-L2.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      S095018 in combination with Sym021 was tested in patients with advanced\/metastatic biliary tract cancers (BTC) whose disease progressed under treatment with at least 1 line of systemic therapy and who had not received prior treatment with PD-(L)1 inhibitors (\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"clintrialgov\" xlink:href=\"NCT04641871\">NCT04641871<\/jats:ext-link>\n                      ). Patients received 3\u2009mg\/kg of Sym021 and 10\u2009mg\/kg of S095018 once every 2 weeks. Primary endpoints included overall response rate and incidence\/severity of adverse events. Key secondary endpoints included pharmacokinetics, immunogenicity assessment, progression-free survival (PFS) and overall survival (OS).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>35 patients with stage IV BTC received S095018 in combination with Sym021. A partial response was achieved in 2 patients (5.7%) and stable disease in 11 patients (31.4%) for a disease control rate of 37%; 4 patients were not evaluable for response. Median PFS and OS were 1.9 months (90% CI 1.8 to 3.7)\u2009and 13.4 months (90%\u2009CI 8.2 to 27.1), respectively. The most common treatment-emergent adverse events of any grade included fatigue, pruritus, infusion-related reaction, and increases in amylase (8.6% each). Exploratory biomarker analyses in paired tumor biopsies showed an increase in intratumoral CD8 T-cell density and an upregulation of gene signatures related to interferon-\u03b3 signaling, antigen presentation, and T-cell activation with treatment without, however, clear association with efficacy endpoints.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Dual PD-1\/TIM-3 inhibition was tolerable but exhibited modest antitumor activity in patients with advanced\/metastatic recurrent BTC who had not received prior anti-PD-(L)1 treatment.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/jitc-2025-012344","type":"journal-article","created":{"date-parts":[[2026,3,13]],"date-time":"2026-03-13T14:30:25Z","timestamp":1773412225000},"page":"e012344","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":4,"title":["Phase Ib multicenter study of anti-TIM-3 (S095018\/Sym023) in combination with anti-PD-1 (Sym021) in patients with advanced\/metastatic recurrent biliary tract cancer"],"prefix":"10.1136","volume":"14","clinical-trial-number":[{"clinical-trial-number":"nct04641871","registry":"10.18810\/clinical-trials-gov"},{"clinical-trial-number":"nct03489343","registry":"10.18810\/clinical-trials-gov"}],"author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5465-8305","authenticated-orcid":false,"given":"Francois","family":"Ghiringhelli","sequence":"first","affiliation":[{"name":"Centre Georges-Francois Leclerc, Dijon, Bourgogne-Franche-Comt\u00e9, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard","family":"Kim","sequence":"additional","affiliation":[{"name":"H Lee Moffitt Cancer Center and Research Institute Department of Gastrointestinal Oncology, Tampa, Florida, 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