When you give that in combination with atezolizumab, it might help stimulate the immune response for MSS disease. The trial itself is being done in a refractory setting, so these are patients who would otherwise be candidates for regorafenib. The randomized phase III comparison was the combination versus atezolizumab alone versus regorafenib.
If patients with MSI-H progress on pembrolizumab and nivolumab, what is the next step of treatment?
For patients with MSI-H disease, they can still have the general standard chemotherapies that are available to them, as well as targeted agents if they progress on checkpoint inhibitor therapy. The checkpoint inhibitors were approved in the refractory setting, so patients had to have at least 2 lines of chemotherapy. If a patient progresses on the checkpoint inhibitor, they could potentially go on to regorafenib, TAS-102, or they could go on to clinical trials. There are many clinical trials that are looking at patients who have had progressive disease on single-agent immunotherapies and [testing whether] combinations make them respond again.
The other big question is, “Where do we use these agents now that they are approved for the treatment of patients with MSI-H CRC? Could they be used in earlier lines of therapy?” Randomized studies are attempting to determine which line of therapy would they see the most benefit.