For patients with unmethylated MGMT
promotors, patients have more aggressive tumors that derive less benefit from TMZ. There is more of an acknowledgment within the neuro-oncology community that we might not need to have temozolomide in the treatment arms at all. This is because when we combine drugs with temozolomide, the combination is toxic and we may not be able to give the experimental drug at a meaningful dose. However, if the experimental drug is potentially better than temozolomide wee would never figure it out because we have always combined treatments with temozolomide. For experimental therapies in patients with unmethylated MGMT
promoters, you are seeing a move in the community now toward not including temozolomide in the experimental arm to give the experimental agent a better chance to succeed without combined toxicity, and that is what we have here.
In summary, all the patients eligible for INSIGhT have IDH
wild-type tumors and unmethylated MGMT
promoters, which means that they have more aggressive tumors that are less responsive to standard of care that include temozolomide.
What was the preclinical evidence for these experimental arms?
There is preclinical evidence from various models for the drugs and phase I has been completed to at least show that the dosing is safe. That is another benefit to not having to combine with temozolomide because a lot of these drugs that come through are ready to go because they are testing in phase I studies in other tumors. By not requiring a combination with temozolomide, we can put patients into these trials earlier.