We are doing this study to find the most effective, safe dose of an experimental drug called rilvegostomig (the study drug). We want to know how well the study drug works on its own and when it is used in combination with another anti-cancer drug called datopotamab deruxtecan (also called Dato-DXd). We will compare how well both of these regimens work versus the standard treatment for non-small cell lung cancer (NSCLC) that is ctDNA-positive.

Non-Small Cell Lung Cancer (NSCLC) that is ctDNA-Positive

Adults ages 18+ who:

• Are diagnosed with NSCLC
• Have not received any treatment yet for their cancer
• Are scheduled or planning to have surgery to remove the tumor
• Have a positive blood test for ctDNA

For more information, contact the study team at annemarie.peters@duke.edu.

If you choose to join this study, we will schedule you to come to our clinic for some screening visits to make sure you are eligible. If you are eligible, you will get a random assignment (like picking numbers from a hat) to 1 of 3 different study groups. Each study group will have a different regimen to follow after surgery.

After you have surgery to remove your tumor, your study group assignment after surgery will be one of the following:

• Group 1: If you are in this group, you will take the study drug in combination with Dato-DXd. You will take the drugs in combination with each other every 3 weeks for 4 cycles, and then you will take only the study drug every 3 weeks for a year.
• Group 2: If you are in this group, you will take the study drug on its own every 3 weeks for a year.
• Group 3: If you are in this group, you will get treatment with the standard therapy. This will involve either chemotherapy or no drug treatment at all, whichever the study doctor believes is the best option for you.

You will return to our clinic for check-ups after your surgery and study group assignment. The frequency and number of these visits will depend on your group assignment.