ABBV-CLS-484 + PD-1 inhibitor

ABBV-CLS-484 + PD-1 inhibitor is an investigational **combination therapy** for cancer immunotherapy, comprising ABBV-CLS-484—a first-in-class, orally bioavailable small molecule inhibitor of the protein tyrosine phosphatases **PTPN2** and **PTPN1**—and a **PD-1 inhibitor** (a monoclonal antibody targeting the programmed cell death protein 1 checkpoint). ABBV-CLS-484 enhances anti-tumor immunity via dual mechanisms: it amplifies tumor-intrinsic responses to interferon and promotes the activation and function of several immune cell types, particularly enhancing JAK–STAT signaling, NK cell and CD8+ T cell cytotoxicity, and reducing T cell exhaustion and dysfunction. The **combination with a PD-1 inhibitor** is under clinical investigation to potentially overcome resistance mechanisms found in PD-1/PD-L1 immune checkpoint blockade in advanced solid tumors, including head and neck squamous cell carcinoma, non-small cell lung cancer, MSI-H tumors, and clear cell renal cell carcinoma[1][2][3][4][5][7][9].