Early Pharmacodynamic Changes Measured Using RNA Sequencing of Peripheral Blood from Patients in a Phase I Study with Mitazalimab, a Potent CD40 Agonistic Monoclonal Antibody

CD40-targeting therapies can enhance the dendritic cell priming of tumor-specific T cells and repolarize intratumoral macrophages to alleviate tumoral immunosuppressive environment remodel extracellular matrix. Mitazalimab is a potent agonistic CD40 monoclonal IgG1 antibody currently under clinical development. This study used RNA sequencing blood samples from subset patients Phase I trial with mitazalimab (NCT02829099) assess peripheral pharmacodynamic activity. We found that induced transient transcriptomic alterations (at 600 µg/kg 900 dose administered intravenously), which mainly were attributed immune activation. In particular, showed reduction in effector (e.g., CD8+ natural killer cells) B peripherally remaining cells, monocytes, showing transcription profiles consistent Lastly, distinct patient subgroups based on pattern could be identified. summary, data presented herein reinforce anticipated mode action support its ongoing