This study compares two treatment options for people with a specific type of colorectal cancer called HER2 positive. This cancer has spread and cannot be removed by surgery. The study aims to find out if a new combination of drugs, including **tucatinib**, works better than the usual treatment. Participants will be randomly placed into two groups: one receiving tucatinib with other drugs (**trastuzumab** and **mFOLFOX6**) and the other receiving standard care, which may include combinations of mFOLFOX6, **bevacizumab**, or **cetuximab**. All these drugs are already used to treat this cancer type.

To participate, you must have HER2 positive colorectal cancer that can't be removed surgically and hasn't been treated with specific therapies before. The study will examine any side effects from these treatments.

• The study involves random assignment to treatment groups.
• Participants may need to provide a tumor sample.
• Previous treatment affects eligibility.