HRS-4508 + trastuzumab + pertuzumab

HRS-4508 + trastuzumab + pertuzumab is a combination therapy under investigation for the treatment of solid tumors. HRS-4508 is a chemical small-molecule drug developed by Jiangsu Hengrui Pharmaceuticals, currently in early-phase clinical trials, primarily for advanced or metastatic solid tumors and non-small cell lung cancer. Trastuzumab and pertuzumab are monoclonal antibodies targeting HER2, frequently used in combination as standard of care in HER2-positive breast cancer and other HER2-driven tumors. Trastuzumab binds to subdomain IV of the HER2 receptor, inhibiting HER2-mediated signaling and eliciting antibody-dependent cellular cytotoxicity (ADCC). Pertuzumab binds to subdomain II of HER2, preventing HER2/HER3 dimerization and downstream signaling. When used together, these antibodies result in dual HER2 blockade and have been shown to synergistically activate the classical complement pathway, enhancing complement-dependent cytotoxicity (CDC) and phagocytosis, in addition to blocking proliferative signaling. The clinical development of this specific combination (HRS-4508 + trastuzumab + pertuzumab) is ongoing, focusing on efficacy, safety, and objective response rate in solid tumors[1][3][5][6][9].