Julius Strauss, MD
Investigators are hopeful that M7824 (MSB0011359C), a bifunctional fusion protein that inhibits the PD-L1 and TGF-β pathways, will improve immune system responses across tumor types. M7824 is composed of an anti-PD-L1 antibody fused to the extracellular domain of TGF-β receptor II, which serves as a “trap” for TGF-β linked to carcinogenesis. Early trial results have been encouraging.
M7824 MECHANISM OF ACTION10
CAF indicates cancer-associated fibroblast; EMT, epithelial-mesenchymal transition; NK, natural killer; TAM, tumor-associated macrophage.
PHASE I TRIAL OF M7824 IN PATIENTS WITH SOLID TUMORS10
Patients will be grouped based on their tumor type, with approximately 30 patients in each cohort. Tumor types include non–small cell lung cancer (NSCLC), colorectal cancer (CRC), and gastric cancer, among others. Patients must have an ECOG performance status of 0 or 1, adequate organ function, and no active central nervous system metastases. The primary endpoints vary depending on the cohort. M7824 is composed of a fully human anti–PD-L1 lgG1 monoclonal antibody linked to the 2 extracellular domains of TGF-β receptor II molecules. The TGF-β receptor II portion serves as a trap for all 3 TGF-β isoforms, and by targeting the tumor with the anti-PD-L1 portion, M7824 may reduce the amount of TGF-β within the tumor micro- environment (FIGURE).2-4
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