{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T04:09:22Z","timestamp":1790309362255,"version":"4.1.0"},"reference-count":22,"publisher":"BMJ","issue":"11","license":[{"start":{"date-parts":[[2023,11,29]],"date-time":"2023-11-29T00:00:00Z","timestamp":1701216000000},"content-version":"unspecified","delay-in-days":28,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100008272","name":"Novartis Pharmaceuticals Corporation","doi-asserted-by":"publisher","award":["N\/A"],"award-info":[{"award-number":["N\/A"]}],"id":[{"id":"10.13039\/100008272","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["J Immunother Cancer"],"accepted":{"date-parts":[[2023,8,28]]},"published-print":{"date-parts":[[2023,11]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>NIS793 is a human IgG2 monoclonal antibody that binds to transforming growth factor beta (TGF-\u03b2). This first-in-human study investigated NIS793 plus spartalizumab treatment in patients with advanced solid tumors.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Patients received NIS793 (0.3\u20131\u2009mg\/kg every 3 weeks (Q3W)) monotherapy; following evaluation of two dose levels, dose escalation continued with NIS793 plus spartalizumab (NIS793 0.3\u201330\u2009mg\/kg Q3W and spartalizumab 300\u2009mg Q3W or NIS793 20\u201330\u2009mg\/kg every 2 weeks [Q2W] and spartalizumab 400\u2009mg every 4 weeks (Q4W)). In dose expansion, patients with non-small cell lung cancer (NSCLC) resistant to prior anti-programmed death ligand 1 or patients with microsatellite stable colorectal cancer (MSS-CRC) were treated at the recommended dose for expansion (RDE).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Sixty patients were treated in dose escalation, 11 with NIS793 monotherapy and 49 with NIS793 plus spartalizumab, and 60 patients were treated in dose expansion (MSS-CRC: n=40; NSCLC: n=20). No dose-limiting toxicities were observed. The RDE was established as NIS793 30\u2009mg\/kg (2100\u2009mg) and spartalizumab 300\u2009mg Q3W. Overall 54 (49.5%) patients experienced \u22651 treatment-related adverse event, most commonly rash (n=16; 13.3%), pruritus (n=10; 8.3%), and fatigue (n=9; 7.5%). Three partial responses were reported: one in renal cell carcinoma (NIS793 30\u2009mg\/kg Q2W plus spartalizumab 400\u2009mg Q4W), and two in the MSS-CRC expansion cohort. Biomarker data showed evidence of target engagement through increased TGF-\u03b2\/NIS793 complexes and depleted active TGF-\u03b2 in peripheral blood. Gene expression analyses in tumor biopsies demonstrated decreased TGF-\u03b2 target genes and signatures and increased immune signatures.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>In patients with advanced solid tumors, proof of mechanism of NIS793 is supported by evidence of target engagement and TGF-\u03b2 pathway inhibition.<\/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\" xlink:href=\"NCT02947165\">NCT02947165<\/jats:ext-link>\n                      .\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/jitc-2023-007353","type":"journal-article","created":{"date-parts":[[2023,11,29]],"date-time":"2023-11-29T13:10:43Z","timestamp":1701263443000},"page":"e007353","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":45,"title":["Phase I\/Ib, open-label, multicenter, dose-escalation study of the anti-TGF-\u03b2 monoclonal antibody, NIS793, in combination with spartalizumab in adult patients with advanced tumors"],"prefix":"10.1136","volume":"11","clinical-trial-number":[{"clinical-trial-number":"nct02947165","registry":"10.18810\/clinical-trials-gov"},{"clinical-trial-number":"nct03436563","registry":"10.18810\/clinical-trials-gov"}],"author":[{"given":"Todd M","family":"Bauer","sequence":"first","affiliation":[{"name":"Sarah Cannon Research Institute, Nashville, Tennessee, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1709-9492","authenticated-orcid":false,"given":"Armando","family":"Santoro","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Italy"},{"name":"Humanitas Cancer Center, IRCCS Humanitas Research Hospital, Rozzano, Lombardia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2573-5789","authenticated-orcid":false,"given":"Chia-Chi","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Oncology, National Taiwan University Hospital, Taipei, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ignacio","family":"Garrido-Laguna","sequence":"additional","affiliation":[{"name":"Division of Oncology, Huntsman Cancer Institute, University of Utah Health, Salt Lake City, Utah, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Markus","family":"Joerger","sequence":"additional","affiliation":[{"name":"Department of Oncology and Hematology, Kantonsspital St Gallen, St. Gallen, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard","family":"Greil","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine III with Haematology, Medical Oncology, Haemostaseology, Infectiology and Rheumatology, Oncologic Center, Salzburg Cancer Research Institute - 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