Jeffrey Skolnik, MD, vice president, clinical development of Inovio Pharmaceuticals Inc Discusses Glioblastoma Treatment in ASCO interview.
MHE: Glioblastoma multiforme or GBM has been one of the most difficult cancers to treat because the characteristics of this disease make it especially resistant to chemotherapy, Inovio’s investigational therapy, INO-5401 combined with immunotherapy, seeks to overcome this challenge. Can you explain why the mechanism of DNA therapy is especially promising in glioblastoma?
Skolnick: So, our DNA medicines are designed to create a robust immune response against, in this case, glioblastoma or GBM. And these responses are dependent upon our DNA medicines, INO-5401, creating antigen specific or protein specific T cells that go and attack the cancer. We are extremely excited about INO-5401 because one, we can see that we are generating these antigen-specific T-cells that are vital to fighting the tumor cells themselves. And I think more importantly, as we will share with the American Society for Clinical Oncology, we're seeing improvement in survival above what we would expect from historical controls. So, we're mostly excited because we have clinical data to say that INO-5401 may very well be working in patients with glioblastoma.
MHE:MGMT promoter methylation status has been identified as a very important biomarker in treating glioblastoma. Can you explain why this biomarker is so important and how it has defined the two cohorts in your study?
Skolnick: Absolutely. So, as you said, promoter methylation status for the MGMT promoter has been prognostic for many years for patients with glioblastoma. And really, one of the things we know is that depending upon your methylation status, may or may not respond to certain types of chemotherapy most specifically, temozolomide. One of the reasons why this is important is because temozolomide is known to have its own side effect profile. One of them is to potentially suppress your immune response by decreasing the number of white blood cells that you have available, for example, to fight the GBM. And so the fact that we were able to show this interim, early book survival. at 12 months approximately 85% in both MGMT promoter unmethylated, the cohort A patients that you mentioned, as well as in our MGMT methylated patients, the cohort B patients that you mentioned, gives us confidence that in both of these subtypes of glioblastoma, we may be able to show a potential clinical benefit.