Immunotherapy + Chemotherapy for Metastatic Colorectal Cancer

This trial aims to evaluate the effectiveness of new treatment combinations for individuals with liver-limited metastatic colorectal cancer, which has spread from the colon to the liver. Participants will receive either a combination of chemotherapy and immunotherapy (including FPV-CV301 and MVA-BN-CV301) or an experimental treatment that incorporates vaccines with standard care. The researchers aim to determine if these treatments can prepare patients for surgery to remove the cancer. Suitable candidates for this trial have metastatic colorectal cancer confined to the liver and are treatment-naïve for stage IV cancer. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group, offering a chance to contribute to significant advancements in cancer care.

The trial protocol does not specify if you need to stop taking your current medications. However, you cannot take certain treatments like corticosteroids or herbal supplements close to the start of the trial. It's best to discuss your specific medications with the trial team.

Research shows that the treatments in this trial have been studied before, and here is what is known about their safety:

1. **FPV-CV301 and MVA-BN-CV301**: Previous studies found that these vaccines usually caused only minor side effects. The initial doses, MVA-BN-CV301, had more common side effects than the booster doses, FPV-CV301, but these were generally mild.

2. **Nivolumab**: This drug is already approved for treating other types of cancer. Research has shown it to be safe, with the most common serious side effects being diarrhea, pneumonia, and urinary infections, occurring in a small number of patients.

3. **mFOLFOX6**: This chemotherapy combination is widely used and considered safe. Studies report low rates of severe side effects, such as nausea or low blood cell counts, with no deaths related to the treatment.

Researchers are excited about these treatments because they combine innovative immunotherapy with standard chemotherapy to tackle metastatic colorectal cancer. Unlike the standard approach that typically involves just chemotherapy with drugs like mFOLFOX6, the experimental arm introduces FPV-CV301 and MVA-BN-CV301, which are designed to boost the immune system's response to cancer cells. By adding these immunotherapies to the regimen, scientists hope to enhance the body’s natural ability to fight the cancer, potentially leading to more effective and long-lasting treatment outcomes. This combination aims to improve the effectiveness of treatment by targeting the cancer more aggressively from multiple angles.

Research shows that the combination of MVA-BN-CV301 and FPV-CV301, which participants in the experimental arm of this trial may receive, targets specific proteins found in many tumors, including those in colorectal cancer. These proteins, CEA and MUC1, are linked to tumor growth. Studies indicate that this combination can effectively trigger an immune response, helping the body attack cancer cells. Earlier trials showed that the vaccine is safe and can activate the immune system. Additionally, the combination of chemotherapy (mFOLFOX6) and the immunotherapy drug Nivolumab, which participants in both arms of this trial will receive, has successfully treated this type of cancer. Together, these treatments aim to boost the body's ability to fight cancer more effectively.¹²⁴⁵⁶