GB1275 + pembrolizumab

GB1275 + pembrolizumab is a combination of a first-in-class, oral small molecule **CD11b modulator** (GB1275) with a **PD-1 immune checkpoint inhibitor** (pembrolizumab). GB1275 reduces myeloid-derived suppressor cells (MDSCs) and tumor-associated macrophages (TAMs), repolarizing M2 immunosuppressive TAMs to an M1 phenotype and increasing CD8+ T cell infiltration, thereby enhancing antitumor immunity. Pembrolizumab is a monoclonal antibody against programmed cell death protein 1 (PD-1), blocking its interaction with ligands PD-L1 and PD-L2 to enhance T-cell mediated immune responses against cancer. The combination is being clinically evaluated for advanced solid tumors, including microsatellite-stable colorectal cancer (MSS-CRC), gastric cancer, metastatic pancreatic ductal adenocarcinoma (mPDAC), triple-negative breast cancer (TNBC), metastatic castration-resistant prostate cancer (mCRPC), and esophageal cancer. This regimen is under investigation in a Phase 1/2 trial (NCT04060342) with ongoing dose escalation and basket expansion arms[1][2][3][4][5].