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GH21 + garsorasib (D-1553) is an investigational combination therapy being developed by Suzhou Genhouse Bio Co., Ltd. for the treatment of advanced solid tumors, specifically those harboring the KRAS G12C mutation such as non-small cell lung cancer (NSCLC). GH21 is a small molecule allosteric inhibitor of Src homology phosphotyrosyl phosphatase 2 (SHP2), a protein that facilitates signaling through the RAS/MAPK pathway. Garsorasib (D-1553) is a potent, selective, and covalent oral inhibitor of KRAS G12C that irreversibly binds to the protein in its inactive GDP-bound state. By combining these two agents, the therapy aims to achieve more complete inhibition of the RAS signaling pathway and overcome adaptive resistance mechanisms that often limit the efficacy of KRAS G12C inhibitor monotherapy. The combination is currently being evaluated in Phase 1b/2 clinical trials for patients who have previously progressed on KRAS G12C inhibitors.
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