zoldonrasib + pembrolizumab

Zoldonrasib + pembrolizumab is an investigational combination regimen being developed for the treatment of RAS G12D-mutated cancers, particularly metastatic non-squamous non-small cell lung cancer (NSCLC). The regimen combines zoldonrasib (RMC-9805), an oral, small-molecule, RAS(ON) G12D-selective covalent tri-complex inhibitor, with pembrolizumab (Keytruda), a humanized IgG4 monoclonal antibody targeting programmed cell death protein 1 (PD-1). Zoldonrasib functions by binding to cyclophilin A to form a binary complex, which then selectively binds to and inhibits the active, GTP-bound state of the mutant RAS G12D protein, preventing downstream oncogenic signaling. Pembrolizumab acts as an immune checkpoint inhibitor, blocking the interaction between PD-1 and its ligands (PD-L1 and PD-L2) to restore T-cell-mediated anti-tumor immune responses. This combination is being evaluated in the Phase 3 RASolve 308 trial as a first-line treatment in combination with platinum-based doublet chemotherapy (pemetrexed plus platinum) for patients with metastatic RAS G12D-mutated non-squamous NSCLC.

Other names

RMC-9805 + MK-3475RMC-9805 + pembrolizumabzoldonrasib + MK-3475zoldonrasib + pembrolizumab + chemotherapyzoldonrasib + pembrolizumab + pemetrexed + platinum chemotherapyzoldonrasib + pembrolizumab + platinum-based chemotherapy