This study examines a treatment for advanced pancreatic cancer, combining **stereotactic body radiotherapy (SBRT)** with two drugs, **defactinib** and **avutometinib**. SBRT is a way to deliver precise radiation to tumors, while the drugs help stop cancer cells from growing. The goal is to see if this combination helps patients live longer without the cancer getting worse. **Key Points:** - **Duration & Visits:** Participation requires regular visits for treatment and monitoring. - **Eligibility:** Patients must have advanced pancreatic cancer, be at least 18, and have tried chemotherapy without success. - **Requirements:** Participants must agree to use birth control and sign a consent form. The study focuses on individuals whose cancer cannot be removed by surgery. Patients must have a good performance status, meaning they are mostly able to care for themselves. They should also have healthy blood and organ function. Certain medications and medical conditions may disqualify individuals from participation. The study is designed to find better ways to treat this challenging condition.