Combination of GNS561 and Trametinib in Patients With Advanced KRAS Mutated Cholangiocarcinoma

This study tests a combination of two drugs — GNS561 and trametinib — in people with advanced bile duct cancer (cholangiocarcinoma) that has a specific genetic mutation called KRAS. These drugs work together to potentially block pathways that help cancer cells survive. **You may be eligible if...** - You have been diagnosed with cholangiocarcinoma inside the liver (intrahepatic) with a confirmed KRAS mutation - You are 18 years or older - Your cancer cannot be cured by surgery or other targeted treatment - You have received one or two prior rounds of chemotherapy - You have at least one measurable tumor on scans - You are in reasonably good physical health (able to carry out daily activities) **You may NOT be eligible if...** - You have previously received a MEK inhibitor or autophagy inhibitor - You have received three or more prior chemotherapy regimens - Your cancer is outside the liver (extrahepatic) in certain locations - You have significant heart problems, eye conditions, lung disease, or uncontrolled infections - You are pregnant or breastfeeding - You have active hepatitis B or C - You are allergic to quinoline-based drugs (e.g., quinine, chloroquine) Talk to your doctor to see if this trial is right for you.