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A combination therapy of D3S-001, an orally administered, next-generation covalent KRAS G12C inhibitor designed for high potency and rapid engagement of the GDP-bound KRAS G12C mutant protein, and pembrolizumab, a monoclonal antibody immune checkpoint inhibitor targeting PD-1. This regimen is under investigation for advanced solid tumors (notably non-small cell lung cancer and colorectal cancer) harboring KRAS p.G12C mutations, particularly in patients resistant to first-generation KRAS G12C inhibitors. D3S-001 provides robust inhibition of KRAS G12C irrespective of nucleotide cycling and is intended to be synergistic with pembrolizumab’s immune-modulating activity. D3S-001 is being developed by D3 Bio, while pembrolizumab is developed and manufactured by Merck. The combination is investigational and administered with D3S-001 orally and pembrolizumab intravenously, as part of ongoing Phase 1/2 clinical trials[1][2][3][4][5][6][7][9][10].
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