Bexmarilimab-induced macrophage activation leads to treatment benefit in solid tumors: The phase I/II first-in-human MATINS trial.
Date
2023-12-19Author
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
Type
Journal Article
Metadata
Show full item recordAbstract
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.
Collections
Subject
Clever-1
GeoMx
Stabilin-1
cancer
first-in-man
immune activation
Humans
Melanoma
Macrophage Activation
Skin Neoplasms
Antibodies, Monoclonal, Humanized
Research team
Clin Trials & Stats Unit
Adult DDU ICR & RM
Language
eng
Date accepted
2023-11-07
License start date
2023-12-19
Citation
Cell Reports Medicine, 2023, 4 (12), pp. 101307 -
Publisher
CELL PRESS