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., 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

: 2023

: Cell Reports Medicine

: 101307

: 4

: 12

: 2666-3791

DOI: https://doi.org/10.1016/j.xcrm.2023.101307

: https://doi.org/10.1016/j.xcrm.2023.101307

: https://research.utu.fi/converis/portal/detail/Publication/380718132

: 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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