A1 Refereed original research article in a scientific journal
Bexmarilimab-induced macrophage activation leads to treatment benefit in solid tumors : The phase I/II first-in-human MATINS trial
Authors: Rannikko Jenna H., Verlingue Loic, de Miguel Maria, Pasanen Annika, Robbrecht Debbie, Skytta Tanja, Iivanainen Sanna, Shetty Shishir, Ma Yuk Ting, Graham Donna M., Arora Sukeshi Patel, Jaakkola Panu, Yap Christina, Xiang Yujuan, Mandelin Jami, Karvonen Matti K., Jalkanen Juho, Karaman Sinem, Koivunen Jussi P., Minchom Anna, Hollmén Maija, Bono Petri
Publisher: Cell Press
Publication year: 2023
Journal: Cell Reports Medicine
Journal name in source: Cell Reports Medicine
Article number: 101307
Volume: 4
Issue: 12
ISSN: 2666-3791
eISSN: 2666-3791
DOI: https://doi.org/10.1016/j.xcrm.2023.101307
Web address : https://doi.org/10.1016/j.xcrm.2023.101307
Self-archived copy’s web address: https://research.utu.fi/converis/portal/detail/Publication/380718132
Preprint address: https://www.medrxiv.org/content/10.1101/2023.04.17.23288693v1
Summary 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.
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