COMMIT: Why is this trial being done?

COMMIT is a trial looking at how safe and effective the immunotherapy treatment Atezolizumab is when given alone, compared to Atezolizumab when combined with FOLFOX6 and Bevacizumab.

Some patients with colorectal cancer have unique features to their cancer called deficient DNA mismatch repair (dMMR) or high levels of microsatellite instability (MSI-H). Patients with these features have cancer that may be particularly susceptible to specific types of immunotherapies that target the PD-1/PD-L1 protein interaction.

It is believed that patients whose cancer has dMMR or MSI-H features are generating an immune response, meaning their immune system recognizes and may be trying to attack the cancer cells. One of the defenses tumors may have is they can express a protein called PD-L1, which when it binds to the protein PD-1 that is expressed on some immune cells, helps shut down this immune system attack. PD-1 and PD-L1 inhibitors are treatments that block this interaction so cancer loses one of its defenses and the immune system may more effectively attack the cancer cells.

Previous studies have demonstrated the superiority of the PD-1 inhibitors Nivolumab or Pembrolizumab when compared to standard chemotherapy combined with either anti-VEGF (Bevacizumab) or anti-EGFR (Panitumumab, Cetuximab) inhibitors as first line treatment for patients with dMMR or MSI-H colorectal cancer. The NCCN now recommends patients with dMMR or MSI-H metastatic colorectal cancer receive first-line treatment with the PD-1 inhibitors Nivolumab or Pembrolizumab.

The COMMIT study is looking at the effectiveness of an immunotherapy called Atezolizumab that blocks the PD-L1 protein. They want to test how safe and effective Atezolizumab is when given alone, compared to when it is given in combination with the chemotherapy regimen FOLFOX6 plus the anti-VEGF inhibitor Bevacizumab.

The use of Atezolizumab, FOLFOX6, and Bevacizumab described here is considered experimental.