Avutometinib and Defactinib in Diffuse Gastric Cancer

There are two main types of stomach cancer based on the appearance under the microscope: intestinal-type and diffuse-type. Some stomach cancers also have a mix of intestinal-type and diffuse-type (mixed type). The participants are being invited to take part in this research study due to having been diagnosed with stomach cancer that has spread to other parts of the body and/or cannot be surgically removed, has diffuse-type or mixed type cells or has gene changes that are associated with diffuse-type stomach cancers (such as mutations in the genes called CDH1 or RHOA), and have already been treated with chemotherapy and the disease is now growing. Defactinib is an oral drug that inhibits the protein focal adhesion kinase (FAK), which has been shown to promote growth of gastric cancer. Avutometinib (also known as VS-6766) is an oral drug that blocks an important signaling pathway in cancer cells known as the MAP kinase pathway. Avutometinib inhibits two proteins in the MAPK kinase pathway, RAF and MEK. The purpose of this study is to determine if the combination study treatment with defactinib and avutometinib is effective in improving the length of time after the start of treatment in which a participant is alive and their cancer does not grow or spread.