Bexmarilimab-induced macrophage activation leads to treatment benefit in solid tumors: The phase I/II first-in-human MATINS trial
Rannikko, Jenna H Verlingue, Loic de Miguel, Maria Pasanen, Annika Robbrecht, Debbie Skytta, Tanja Iivanainen, Sanna Shetty, Shishir Ma, Yuk Ting Graham, Donna M
Rannikko, Jenna H
Verlingue, Loic
de Miguel, Maria
Pasanen, Annika
Robbrecht, Debbie
Skytta, Tanja
Iivanainen, Sanna
Shetty, Shishir
Ma, Yuk Ting
Graham, Donna M
Citations
Altmetric:
Affiliation
Other Contributors
Publication date
2023-12-05
Subject
Collections
Research Projects
Organizational Units
Journal Issue
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.
Citation
Rannikko JH, Verlingue L, de Miguel M, Pasanen A, Robbrecht D, Skytta T, Iivanainen S, Shetty S, Ma YT, Graham DM, Arora SP, Jaakkola P, Yap C, Xiang Y, Mandelin J, Karvonen MK, Jalkanen J, Karaman S, Koivunen JP, Minchom A, Hollmén M, Bono P. Bexmarilimab-induced macrophage activation leads to treatment benefit in solid tumors: The phase I/II first-in-human MATINS trial. Cell Rep Med. 2023 Dec 19;4(12):101307. doi: 10.1016/j.xcrm.2023.101307. Epub 2023 Dec 5.
Type
Article