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Bexmarilimab-induced macrophage activation leads to treatment benefit in solid tumors: the phase I/II first-in-human MATINS trial
Rannikko, J. H. Verlingue, L. de Miguel, M. Pasanen, A. Robbrecht, D. Skytta, T. Iivanainen, S. Shetty, S. Ma, Y. T. Graham, Donna M
Rannikko, J. H.
Verlingue, L.
de Miguel, M.
Pasanen, A.
Robbrecht, D.
Skytta, T.
Iivanainen, S.
Shetty, S.
Ma, Y. T.
Graham, Donna M
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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.
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Date
2023
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Article
Citation
Rannikko JH, Verlingue L, de Miguel M, Pasanen A, Robbrecht D, Skytta T, et al. Bexmarilimab-induced macrophage activation leads to treatment benefit in solid tumors: The phase I/II first-in-human MATINS trial. Cell reports Medicine. 2023 Dec 19;4(12):101307. PubMed PMID: 38056464. Pubmed Central PMCID: PMC10772343. Epub 2023/12/07. eng.