This clinical trial is focused on studying a type of cancer called metastatic colorectal cancer, which is a form of cancer that starts in the colon or rectum and has spread to other parts of the body. The study is testing a new treatment combination that includes three medications: azenosertib (also known as ZN-c3), encorafenib, and cetuximab. Azenosertib is a small-molecule inhibitor, which means it is designed to block certain proteins that help cancer cells grow. Encorafenib is a BRAF V600-mutant kinase inhibitor, which targets specific mutations in cancer cells, and cetuximab is a solution for infusion that works by blocking a protein on the surface of cancer cells.

The purpose of this study is to find the best dose of azenosertib when used in combination with encorafenib and cetuximab. The study will also look at how well this combination works in treating metastatic colorectal cancer. Participants in the study will receive these medications and will be monitored by healthcare professionals. Some participants may receive a placebo, which is a substance with no active medication, to compare the effects of the treatment. The study will take place over several phases, starting with a dose-escalation phase to determine the safest and most effective dose, followed by an expansion phase to further evaluate the treatment’s effectiveness.

Throughout the study, participants will have regular check-ups, including blood tests and scans, to monitor their health and the cancer’s response to the treatment. The study aims to provide valuable information on the potential benefits and safety of this new treatment combination for people with metastatic colorectal cancer. The trial is expected to continue until the end of 2026, with recruitment having started in July 2023.