dc.contributor.author | Rannikko, JH | |
dc.contributor.author | Verlingue, L | |
dc.contributor.author | de Miguel, M | |
dc.contributor.author | Pasanen, A | |
dc.contributor.author | Robbrecht, D | |
dc.contributor.author | Skytta, T | |
dc.contributor.author | Iivanainen, S | |
dc.contributor.author | Shetty, S | |
dc.contributor.author | Ma, YT | |
dc.contributor.author | Graham, DM | |
dc.contributor.author | Arora, SP | |
dc.contributor.author | Jaakkola, P | |
dc.contributor.author | Yap, C | |
dc.contributor.author | Xiang, Y | |
dc.contributor.author | Mandelin, J | |
dc.contributor.author | Karvonen, MK | |
dc.contributor.author | Jalkanen, J | |
dc.contributor.author | Karaman, S | |
dc.contributor.author | Koivunen, JP | |
dc.contributor.author | Minchom, A | |
dc.contributor.author | Hollmén, M | |
dc.contributor.author | Bono, P | |
dc.coverage.spatial | United States | |
dc.date.accessioned | 2024-01-08T11:38:07Z | |
dc.date.available | 2024-01-08T11:38:07Z | |
dc.date.issued | 2023-12-19 | |
dc.identifier | 101307 | |
dc.identifier | S2666-3791(23)00501-3 | |
dc.identifier.citation | Cell Reports Medicine, 2023, 4 (12), pp. 101307 - | |
dc.identifier.issn | 2666-3791 | |
dc.identifier.uri | https://repository.icr.ac.uk/handle/internal/6097 | |
dc.identifier.eissn | 2666-3791 | |
dc.identifier.eissn | 2666-3791 | |
dc.identifier.doi | 10.1016/j.xcrm.2023.101307 | |
dc.identifier.doi | 10.1016/j.xcrm.2023.101307 | |
dc.description.abstract | Macrophage Clever-1 contributes to impaired antigen presentation and suppression of anti-tumor immunity. This first-in-human trial investigates the safety and tolerability of Clever-1 blockade with bexmarilimab in patients with treatment-refractory solid tumors and assesses preliminary anti-tumor efficacy, pharmacodynamics, and immunologic correlates. Bexmarilimab shows no dose-limiting toxicities in part I (n = 30) and no additional safety signals in part II (n = 108). Disease control (DC) rates of 25%-40% are observed in cutaneous melanoma, gastric, hepatocellular, estrogen receptor-positive breast, and biliary tract cancers. DC associates with improved survival in a landmark analysis and correlates with high pre-treatment intratumoral Clever-1 positivity and increasing on-treatment serum interferon γ (IFNγ) levels. Spatial transcriptomics profiling of DC and non-DC tumors demonstrates bexmarilimab-induced macrophage activation and stimulation of IFNγ and T cell receptor signaling selectively in DC patients. These data suggest that bexmarilimab therapy is well tolerated and show that macrophage targeting can promote immune activation and tumor control in late-stage cancer. | |
dc.format | Print-Electronic | |
dc.format.extent | 101307 - | |
dc.language | eng | |
dc.language.iso | eng | |
dc.publisher | CELL PRESS | |
dc.relation.ispartof | Cell Reports Medicine | |
dc.rights.uri | https://creativecommons.org/licenses/by-nc-nd/4.0/ | |
dc.subject | Clever-1 | |
dc.subject | GeoMx | |
dc.subject | Stabilin-1 | |
dc.subject | cancer | |
dc.subject | first-in-man | |
dc.subject | immune activation | |
dc.subject | Humans | |
dc.subject | Melanoma | |
dc.subject | Macrophage Activation | |
dc.subject | Skin Neoplasms | |
dc.subject | Antibodies, Monoclonal, Humanized | |
dc.title | Bexmarilimab-induced macrophage activation leads to treatment benefit in solid tumors: The phase I/II first-in-human MATINS trial. | |
dc.type | Journal Article | |
dcterms.dateAccepted | 2023-11-07 | |
dc.date.updated | 2024-01-03T00:53:05Z | |
rioxxterms.version | VoR | |
rioxxterms.versionofrecord | 10.1016/j.xcrm.2023.101307 | |
rioxxterms.licenseref.startdate | 2023-12-19 | |
rioxxterms.type | Journal Article/Review | |
pubs.author-url | https://www.ncbi.nlm.nih.gov/pubmed/38056464 | |
pubs.issue | 12 | |
pubs.organisational-group | ICR | |
pubs.organisational-group | ICR/Primary Group | |
pubs.organisational-group | ICR/Primary Group/ICR Divisions | |
pubs.organisational-group | ICR/Primary Group/ICR Divisions/Clinical Studies | |
pubs.organisational-group | ICR/Primary Group/ICR Divisions/Clinical Studies/Clinical Trials & Statistics Unit | |
pubs.organisational-group | ICR/Primary Group/ICR Divisions/Clinical Studies/The Adult Drug Development Unit at the ICR and the RM | |
pubs.publication-status | Published | |
pubs.publisher-url | http://dx.doi.org/10.1016/j.xcrm.2023.101307 | |
pubs.volume | 4 | |
icr.researchteam | Clin Trials & Stats Unit | |
icr.researchteam | Adult DDU ICR & RM | |
dc.contributor.icrauthor | Yap, Christina | |
dc.contributor.icrauthor | Minchom, Anna | |
icr.provenance | Deposited by Prof Christina Yap on 2024-01-03. Deposit type is initial. No. of files: 1. Files: MATINS trial publication Cell Reports.pdf | |