This study involves people with metastatic colorectal cancer, which is cancer that started in the colon or rectum and has spread to other parts of the body. The study will test a treatment that combines ivonescimab, an experimental medication also known by the code names AK112 or SMT112, with a chemotherapy regimen called FOLFOX. FOLFOX consists of three medications: fluorouracil, oxaliplatin, and folinic acid. This combination will be compared to another treatment that uses bevacizumab combined with the same FOLFOX chemotherapy. The purpose of the study is to compare how long patients live without their cancer getting worse when treated with ivonescimab plus FOLFOX compared to bevacizumab plus FOLFOX.

Participants in this study will be randomly assigned to receive either ivonescimab or bevacizumab, both given in combination with FOLFOX chemotherapy. The study is designed so that neither the participants nor their doctors will know which treatment is being given, which helps ensure fair comparison of the results. The medications will be given through a vein, which means they are delivered directly into the bloodstream through an intravenous line. During the study, participants will have regular check-ups where doctors will monitor the size of tumors using imaging scans and assess how well the treatment is working. The study will also track any side effects that occur and measure the levels of ivonescimab in the blood at different times.

The study will also collect information about how long participants live overall, how many people respond to treatment, and how long those responses last. Doctors will monitor for any unwanted effects from the medications and check blood tests for abnormal results. For those receiving ivonescimab, the study will also check whether the body develops antibodies against this medication, which could affect how well it works. This study is intended for people who have not yet received treatment for their metastatic colorectal cancer, though previous treatment for earlier stages of the disease is allowed if it was completed more than twelve months before the cancer spread.