RMC-9805 + gemcitabine + nab-paclitaxel

RMC-9805 + gemcitabine + nab-paclitaxel is an investigational combination regimen composed of three agents: - **RMC-9805**, an orally bioavailable, covalent tricomplex inhibitor specifically designed to target the active (GTP-bound) KRAS G12D mutant. It operates as a molecular glue by first non-covalently binding cyclophilin A, then irreversibly binding to KRASG12D(ON) at the Asp12 residue, thereby blocking KRAS G12D-mediated signaling and subsequent tumor cell survival pathways. This can lead to apoptosis and may help revert immune-evasive mechanisms in KRASG12D-mutant cancers[1][2][3][4][5][6][7][8]. - **Gemcitabine**, a nucleoside analog and antimetabolite that disrupts DNA synthesis by incorporation into DNA and inhibition of DNA polymerase. - **Nab-paclitaxel** (nanoparticle albumin-bound paclitaxel), a cytotoxic taxane that stabilizes microtubules and inhibits cell division. The combination is primarily being explored for advanced solid tumors, notably pancreatic ductal adenocarcinomas (PDAC) harboring the KRAS G12D mutation in early-phase clinical trials[3][4][5][8]. RMC-9805 is developed by Revolution Medicines and is currently in phase 1/1b for KRAS G12D-mutated solid tumors. It shows potential for synergy with immune therapies (e.g., PD-1 inhibitors) and cytotoxic chemotherapy such as gemcitabine + nab-paclitaxel[2][3][7]. Gemcitabine and nab-paclitaxel are widely used chemotherapy agents, particularly in PDAC.

Other names

RMC-9805 + gemcitabine + nab-paclitaxel