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

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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Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.

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Declaration of interests L.V. declares consulting fees from Adaptherapy; stock or stock options for Resolved. M.D.M. declares payment or honoraria for lectures, presentations, speakers bureaus, and manuscript writing or educational events from Janssen and MSD. A.P. declares payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Incyte and Roche; support for attending meetings and/or travel from Gilead; participation on a Data Safety Monitoring Board or Advisory Board for Incyte, Novartis, Gilead, and BeiGen. D.B. declares consulting fees from Merck AG, Pfizer, Bayer, Cantargia AB, Faron Pharmaceuticals, and Servier. T.S. declares payment or honoraria for lectures, presentations, speakers bureaus, and manuscript writing or educational events from BMS; participation on a Data Safety Monitoring Board or Advisory Board for Faron Pharmaceuticals, Merck, and Novartis; leadership or fiduciary role in other board, society, committee or advocacy group, paid or unpaid for Finnish Oncology Society. S.I. declares grants or contracts from any entity from Roche and AstraZeneca; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from BMS, Roche, Astra Zeneca, Takeda, Novartis, MSD, Pierre Fabre, and Boehringer-Ingelheim. S.S. declares consulting fees from Faron Pharmaceuticals, participation on a Data Safety Monitoring Board or Advisory Board for Faron Pharmaceuticals. Y.T.M. declares consulting fees from Eisai, Roche, AstraZeneca, and Ipsen; payment or honoraria for lectures, presentations, speakers bureaus, and manuscript writing or educational events for Bayer and Boston Scientific; and participation on a Data Safety Monitoring Board or Advisory Board for Faron Pharmaceuticals. D.G. declares consulting fees from Clinigen and McCann Health; payment or honoraria for lectures, presentations, speakers bureaus, and manuscript writing or educational events from Cancer Drug Development Fund and Pfizer. S.P.A. declares payment or honoraria for lectures, presentations, speakers bureaus, and manuscript writing or educational events from Bayer, BMS, ASCO, and Exelixis; participation on a Data Safety Monitoring Board or Advisory Board for AstraZeneca, Seagen, and QED Therapeutics/Helsinn; leadership or fiduciary role in other board, society, committee or advocacy group, paid or unpaid for Board-Support New India. P.J. declares participation on a Data Safety Monitoring Board or Advisory Board for Faron Pharmaceuticals. C.Y. declares consulting fees from Faron Pharmaceuticals; and payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Bayer. J.M. declares all support for the present manuscript from Faron Pharmaceuticals (employment); patents planned, issued or pending for Faron Pharmaceuticals; participation on a Data Safety Monitoring Board or Advisory Board for Faron Pharmaceuticals; and stock or stock options for Faron Pharmaceuticals. M.K.K. declares all support for the present manuscript from Faron Pharmaceuticals (employment); patents planned, issued or pending for Faron Pharmaceuticals; and stock or stock options for Faron Pharmaceuticals. J.J. declares all support for the present manuscript from Faron Pharmaceuticals (employment); grants or contracts from any entity from European Innovation Council; and stock or stock options for Faron Pharmaceuticals. J.P.K. declares all support for the present manuscript from Faron Pharmaceuticals; consulting fees from MSD, BMS, Roche, Pfizer, and AstraZeneca; payment or honoraria for lectures, presentations, speakers bureaus, and manuscript writing or educational events from MSD, BMS, Roche, AstraZeneca, and Sanofi; payment for expert testimony from Sanofi; support for attending meetings and/or travel from BMS; participation on a Data Safety Monitoring Board or Advisory Board for Faron Pharmaceuticals; and stock or stock options from Faron Pharmaceuticals. A.M. declares payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Janssen, Chugai, Novartis, and Bayer; support for attending meetings and/or travel from Amgen; and participation on a Data Safety Monitoring Board or Advisory Board for Janssen, Takeda, Genmab, Merck, and Faron Pharmaceuticals. M.H. declares all support for the present manuscript from Faron Pharmaceuticals; patents issued or pending for Faron Pharmaceuticals; and stock or stock options from Faron Pharmaceuticals. P.B. declares consulting fees from Faron Pharmaceuticals, Herantis Pharma, MSD Oncology, Ipsen, Oncorena, and TILT biotherapeutics; participation on a Data Safety Monitoring Board or Advisory Board for Faron Pharmaceuticals, TILT biotherapeutics, and Oncorena; leadership or fiduciary role in other board, society, committee or advocacy group, paid or unpaid for Terveystalo (employment); stock or stock options for Terveystalo, TILT biotherapeutics; and other financial or non-financial interests for Faron pharmaceuticals, stock ownership (spouse).