imatinib + trametinib

This combination therapy consists of the MEK inhibitor trametinib and the tyrosine kinase inhibitor imatinib. It is currently being evaluated in a Phase 1 pilot trial (NCT06962254) led by China Medical University Hospital for the treatment of unresectable solid tumors harboring KRAS mutations, particularly non-G12C variants. Trametinib targets MEK1 and MEK2 within the MAPK signaling pathway, while imatinib, primarily known as a BCR-ABL inhibitor, also targets PDGFR and c-KIT. The rationale for this combination is to overcome adaptive resistance; MEK inhibition often triggers a feedback loop that increases PDGFR expression, which imatinib can block to enhance anti-tumor activity. Preclinical data suggests this regimen may be particularly effective in KRAS-mutant pancreatic adenocarcinoma, showing superior effects compared to direct KRAS G12C inhibitors in certain models.

Brand names

GleevecMekinist

Other names

imatinib and trametinibtrametinib and imatinib