GI-102 + trastuzumab deruxtecan

GI-102 + trastuzumab deruxtecan is an investigational combination therapy currently in phase 1/2 clinical development for advanced and/or metastatic solid tumors, including renal cell carcinoma, melanoma, breast, and other cancers. **GI-102** is a novel bi-specific Fc fusion protein composed of a CD80 ectodomain (N-terminal) and an interleukin-2 (IL-2) variant (C-terminal) attached via a human IgG4 Fc. It targets both CD80 and IL2Rβγ: the CD80 domain blocks immune-suppressive CTLA-4 on regulatory T cells (Tregs) and the IL-2 variant is engineered to abolish binding to IL-2Rα, thereby selectively stimulating NK and CD8+ T cell proliferation and activity, while minimizing Treg activation. **Trastuzumab deruxtecan (T-DXd, Enhertu)** is a HER2-directed antibody-drug conjugate consisting of a humanized anti-HER2 IgG1 monoclonal antibody linked via a cleavable peptide to the cytotoxic topoisomerase I inhibitor deruxtecan (DXd). It binds HER2 on cancer cells, internalizes, and releases DXd intracellularly, causing DNA damage and apoptosis. This combination aims to enhance anti-tumor immune activity and deliver targeted cytotoxicity to HER2-expressing tumors.

Brand names

Enhertu

Other names

fam-trastuzumab deruxtecan-nxki