In this study, people will be placed into one of three groups by chance. One group will receive a medicine called zanzalintinib by mouth every day and another medicine called MK 3475A as an injection every three weeks. A second group will receive only zanzalintinib each day. The third group will receive a placebo pill that looks like zanzalintinib but has no active medicine. People in the second and third groups will not know which one they are receiving.

During the study, participants will have regular clinic visits and medical tests to check their health and how well the treatment is working. The study medicine may be given for up to two years, and participants may be followed for up to five years so researchers can continue to monitor their health and study results.

Stage II or III colorectal cancer with signs of residual microscopic disease following standard treatment.

People may be able to join this study if they have Stage II or Stage III colon or rectal cancer that has been confirmed by tissue testing. Their cancer must have certain test results that show specific features of the tumor. They must have had surgery that removed all visible cancer and completed at least three months of chemotherapy that included oxaliplatin before surgery, after surgery, or both. Researchers are studying ways to help keep the cancer from coming back after treatment.

This study is looking at people who have had treatment for colorectal cancer but may still have tiny amounts of cancer left in their body that can only be found with special blood tests. Researchers want to learn if a medicine called zanzalintinib, given by itself or together with another medicine called MK 3475A, can help keep the cancer from coming back.

The study will compare different treatment groups to see which approach works best. Researchers will also use blood tests to measure small pieces of tumor DNA in the blood and see if the treatments lower these levels. The goal is to find out if these medicines can help people stay cancer free for a longer time after treatment.