A Study to Evaluate the Efficacy of VVD-133214 in Combination With Pembrolizumab Compared With Pembrolizumab Alone in Participants With Advanced Cancer of the Colon or Rectum

Researchers are looking for a better way to treat people with advanced colorectal cancer. Colorectal cancer (cancer of the colon or rectum) is one of the most common cancers worldwide. Treatments include surgery, chemotherapy, radiotherapy, and immunotherapy; however, these treatments do not work for everyone, may cause serious adverse events or may stop working eventually. New treatments and treatment combinations are needed, especially for cancers that cannot be removed with surgery or that have spread to other parts of the body (called advanced or metastatic cancer). Cells normally repair themselves when mistakes happen as they divide. But in some people with cancer, the repair system does not work properly because of a problem called dMMR (deficient mismatch repair). As a result, mistakes build up in the cell's DNA, leading to a condition called MSI (microsatellite instability). Over time, these changes can cause cells to grow and behave abnormally, contributing to the development and growth of cancer. To survive, some cancer cells with dMMR or MSI rely on a protein called Werner helicase. This protein helps repair some of the DNA damage allowing them to keep growing. Because these cancer cells depend more on Werner helicase than healthy cells, blocking this protein may help stop cancer cells from surviving while having less effect on healthy cells. The study drug, VVD-133214, is designed to block the Werner helicase protein. Blocking this protein may help stop cancer cells from growing, while causing less harm to healthy cells. VVD-133214 is being studied in combination with pembrolizumab, an approved immunotherapy that helps the immune system recognize and attack cancer cells. This study will test the combination of VVD-133214 and pembrolizumab in people with advanced colorectal cancer with MSI and/or dMMR who have not yet received treatment for their advanced disease. The study aims to find the best dose of VVD-133214 in combination with pembrolizumab an