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**Ribociclib + trametinib** is a combination of two small molecule targeted cancer therapies: ribociclib, a selective cyclin-dependent kinase 4/6 (CDK4/6) inhibitor, and trametinib, a MEK1/2 inhibitor. The mechanistic rationale is to simultaneously block cell cycle progression and mitogenic signaling, potentially providing synergistic antitumor effects. Ribociclib is developed and marketed under the brand name Kisqali by Novartis, and trametinib is developed and marketed as Mekinist by Novartis. This combination has been evaluated in clinical studies, including a Phase Ib trial in patients with metastatic or advanced solid tumors, with particular interest in advanced pancreatic adenocarcinoma and KRAS-mutant colorectal cancer. Clinical studies did not proceed to Phase II due to strategic reasons not related to safety[1][3][5]. Preclinical data also suggests potential utility in neuroendocrine tumors[4].
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