dabrafenib + trametinib + TNO155

This is a **combination therapy** comprising **dabrafenib**, **trametinib**, and **TNO155**. Dabrafenib is a small molecule inhibitor of mutant BRAF kinase, trametinib is a small molecule inhibitor of MEK1/2, and TNO155 is a selective SHP2 (Src homology region 2 domain-containing phosphatase-2) inhibitor. The combination is being investigated in clinical trials for treatment of advanced or metastatic cancers with **BRAF V600 mutations**, including colorectal cancer. Targeting the MAPK signaling pathway at multiple nodes (BRAF, MEK, SHP2), this combination is designed to enhance antitumor activity, delay or overcome resistance to BRAF/MEK inhibitor therapy, and provide synergistic cancer cell growth inhibition. TNO155, by inhibiting SHP2, is believed to block upstream RAS-mediated MAPK reactivation, a common resistance mechanism to BRAF/MEK inhibitors. This triplet is currently in early-phase clinical studies for BRAF-mutant solid tumors, particularly colorectal cancer.