Bexmarilimab-induced macrophage activation leads to treatment benefit in solid tumors: The phase I/II first-in-human MATINS trial

Jenna H. Rannikko, Loic Verlingue, Maria de Miguel, Annika Pasanen, Debbie Robbrecht, Tanja Skytta, Sanna Iivanainen, Shishir Shetty, Yuk Ting Ma, Donna M. Graham, Sukeshi Patel Arora, Panu Jaakkola, Christina Yap, Yujuan Xiang, Jami Mandelin, Matti K. Karvonen, Juho Jalkanen, Sinem Karaman, Jussi P. Koivunen, Anna MinchomMaija Hollmén, Petri Bono

Research output: Contribution to journalArticlepeer-review

3 Scopus citations

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.

Original languageEnglish (US)
Article number101307
JournalCell Reports Medicine
Volume4
Issue number12
DOIs
StatePublished - Dec 19 2023
Externally publishedYes

Keywords

  • Clever-1
  • GeoMx
  • Stabilin-1
  • cancer
  • first-in-man
  • immune activation

ASJC Scopus subject areas

  • General Biochemistry, Genetics and Molecular Biology

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