RMC-9805

RMC-9805 Medication Report

Name: RMC-9805 Name (English): RMC-9805

Mechanism of Action: RMC-9805 is an orally bioavailable covalent tri-complex inhibitor that selectively targets the active, GTP-bound form of the KRAS G12D mutation (KRASG12D(ON)). Upon oral administration, RMC-9805 first non-covalently binds to cyclophilin A, forming a binary complex. This complex then covalently and irreversibly binds to the KRASG12D(ON) protein at the Asp-12 residue. This interaction prevents KRAS G12D-mediated signaling and the activation of downstream survival pathways, leading to apoptosis in tumor cells expressing this mutation. Additionally, RMC-9805 may abrogate the suppressive tumor microenvironment and enhance anti-tumor immune responses.

Indications and Usage: RMC-9805 is an investigational drug currently being evaluated in Phase 1 clinical trials for the treatment of advanced solid tumors harboring the KRAS G12D mutation. Preliminary data suggest potential activity in:

• Non-small cell lung cancer (NSCLC)
• Pancreatic ductal adenocarcinoma (PDAC)
• Colorectal cancer (CRC)

Clinical Trial Information: RMC-9805 is being investigated in several Phase 1/1b clinical trials, including:

• NCT06040541: A multicenter, open-label study evaluating the safety, tolerability, pharmacokinetics, and preliminary antitumor activity of RMC-9805 as monotherapy and in combination with RMC-6236 in adults with KRAS G12D-mutant solid tumors.
• Other platform studies are evaluating RMC-9805 in combination with standard-of-care therapies or other novel agents in gastrointestinal solid tumors and advanced RAS-mutated NSCLC.