{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,8]],"date-time":"2026-06-08T12:14:23Z","timestamp":1780920863487,"version":"3.54.1"},"reference-count":28,"publisher":"BMJ","issue":"6","license":[{"start":{"date-parts":[[2026,6,8]],"date-time":"2026-06-08T00:00:00Z","timestamp":1780876800000},"content-version":"unspecified","delay-in-days":7,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"Kymab, a Sanofi Company","award":["NA"],"award-info":[{"award-number":["NA"]}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["J Immunother Cancer"],"accepted":{"date-parts":[[2026,4,27]]},"published-print":{"date-parts":[[2026,6]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Immunosuppression mechanisms mediated by regulatory T cells (T\n                      <jats:sub>regs<\/jats:sub>\n                      ) can lead to poor clinical outcomes in patients undergoing immune-based therapies. Activation markers, such as inducible T-cell co-stimulator (ICOS), are highly expressed on the surface of tumor-infiltrating T\n                      <jats:sub>regs<\/jats:sub>\n                      and present as relevant targets for targeted depletion of these cells. Here, we present clinical outcomes from a Phase 1 study (\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"clintrialgov\" xlink:href=\"NCT03829501\">NCT03829501<\/jats:ext-link>\n                      ) of an anti-ICOS antibody of alomfilimab (SAR445256 or KY1044) as monotherapy and in combination with the anti-programmed death-ligand 1 (PD-L1) antibody, atezolizumab, in patients with advanced solid tumors.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Alomfilimab was administered intravenously once every 3\u2009weeks (Q3W) \u00b13\u2009days at six dose levels (DLs; 0.8 mg to 240\u2009mg) as monotherapy and five DLs (0.8 mg to 80\u2009mg) in combination with atezolizumab (1,200\u2009mg Q3W \u00b13\u2009days). Eligible patients must have had advanced metastatic disease as determined by Response Evaluation Criteria in Solid Tumors V.1.1 and no viable treatment options according to National Comprehensive Cancer Network guidelines.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Overall 38 patients were enrolled in the monotherapy cohort, and 102 patients were enrolled in the combination therapy cohort. Alomfilimab had a manageable safety profile and showed a trend toward modest efficacy in tumor growth control when combined with anti-PD-L1 in selected malignancies. At least one treatment-emergent adverse event was reported in 35 patients (89.7%) in the monotherapy cohort, and in 99 (98%) patients in the combination cohort. Objective response was not observed in the monotherapy cohort. In the combination cohort, seven patients had an objective response. Median time to progression-free survival was 2 months for both cohorts. Furthermore, alomfilimab showed evidence of target engagement on T-cell subsets, specifically cluster of differentiation (CD)4+memory cells, in both single-agent and in combination treatment with atezolizumab. This was accompanied by transient elevation of granulocyte-macrophage colony-stimulating factor, interferon-\u03b3, and tumor necrosis factor-\u03b1 levels and dose-dependent reduction of ICOS+T\n                      <jats:sub>regs<\/jats:sub>\n                      in the tumor microenvironment.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      Alomfilimab treatment was associated with an acceptable safety profile across both mono and combination approaches, accompanied by decreased ICOS+T\n                      <jats:sub>regs<\/jats:sub>\n                      populations and enhanced CD4+ and\u2009CD8+ effector T cells\u2009cell activity. Limited clinical activity was observed despite evidence of biological activity.\n                    <\/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=\"NCT03829501\">NCT03829501<\/jats:ext-link>\n                      .\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/jitc-2025-013540","type":"journal-article","created":{"date-parts":[[2026,6,8]],"date-time":"2026-06-08T11:55:12Z","timestamp":1780919712000},"page":"e013540","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":0,"title":["First-in-human, phase 1, open-label study of alomfilimab, an anti-ICOS antibody, as a single agent and in combination with anti-PD-L1 in advanced malignancies"],"prefix":"10.1136","volume":"14","clinical-trial-number":[{"clinical-trial-number":"nct03829501","registry":"10.18810\/clinical-trials-gov"},{"clinical-trial-number":"nct03829501","registry":"10.18810\/clinical-trials-gov"},{"clinical-trial-number":"nct03829501","registry":"10.18810\/clinical-trials-gov"}],"author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4803-8513","authenticated-orcid":false,"given":"Aung","family":"Naing","sequence":"first","affiliation":[{"name":"Department of Investigational Cancer Therapeutics, MD Anderson Cancer Center, The University of Texas, Houston, Texas, USA"}],"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":"National Taiwan University Hospital, Taipei City, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manish R","family":"Patel","sequence":"additional","affiliation":[{"name":"Florida Cancer Specialists\/Sarah Cannon Research Institute, Sarasota, Florida, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giuseppe","family":"Curigliano","sequence":"additional","affiliation":[{"name":"Istituto Europeo di Oncologia Biblioteca IRCCS, Milan, Lombardy, Italy"},{"name":"Medical Oncology and Hematology Department, University of Milan, Milan, Lombardy, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Howard A.","family":"Burris","sequence":"additional","affiliation":[{"name":"Sarah Cannon Research Institute LLC, Nashville, Tennessee, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fiona","family":"Thistlethwaite","sequence":"additional","affiliation":[{"name":"Advanced Immunotherapy and Cell Therapy Team, Department of Medical Oncology, The Christie NHS Foundation Trust, Manchester, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0103-730X","authenticated-orcid":false,"given":"Filippo","family":"De Braud","sequence":"additional","affiliation":[{"name":"Medical Oncology and Hematology Department, University of Milan, Milan, Lombardy, Italy"},{"name":"Department of Medical Oncology and Hematology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, Lombardia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9339-7101","authenticated-orcid":false,"given":"Anna","family":"Minchom","sequence":"additional","affiliation":[{"name":"Drug Development Unit, Royal Marsden Hospital, The Institute of Cancer Research - Sutton, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8322-475X","authenticated-orcid":false,"given":"Paolo A","family":"Ascierto","sequence":"additional","affiliation":[{"name":"Melanoma, Cancer Immunotherapy and Development Therapeutics, Istituto Nazionale Tumori IRCCS Fondazione Pascale, Napoli, Italy"},{"name":"Universita degli Studi di Napoli Federico II, Naples, Campania, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew","family":"Wake","sequence":"additional","affiliation":[{"name":"Kymab, a Sanofi Company, Babraham Research Campus, Cambridge, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mai A","family":"Nguyen","sequence":"additional","affiliation":[{"name":"Sanofi, Frankfurt, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giovanni","family":"Abbadessa","sequence":"additional","affiliation":[{"name":"Sanofi, Research and Development, Sanofi, Morristown, New Jersey, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard C A","family":"Sainson","sequence":"additional","affiliation":[{"name":"Kymab, a Sanofi Company, Babraham Research Campus, Cambridge, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cintia C","family":"Palu","sequence":"additional","affiliation":[{"name":"Sanofi, Cambridge, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sonia","family":"Quaratino","sequence":"additional","affiliation":[{"name":"Kymab, a Sanofi Company, Babraham Research Campus, Cambridge, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cecilia","family":"Deantonio","sequence":"additional","affiliation":[{"name":"Sanofi, Cambridge, 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Inhibitor Response In Advanced Malignancies: A Systematic Review And Meta-Analysis Of Overall Survival Data.","volume":"50","author":"Wallis","year":"2020","journal-title":"Jpn J Clin Oncol"},{"key":"2026060804550570000_14.6.e013540.28","doi-asserted-by":"crossref","DOI":"10.3390\/cells12131787","article-title":"Lighting Up the Fire in the Microenvironment of Cold Tumors: A Major Challenge to Improve Cancer Immunotherapy","volume":"12","author":"Benoit","year":"2023","journal-title":"Cells"}],"container-title":["Journal for ImmunoTherapy of 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