Updated results from an initial phase 1 study of the work using the IL-12 inducible therapy as a monotherapy (ClinicalTrials.gov Identifier: NCT02026271) and a dose-escalation substudy in combination with nivolumab (ClinicalTrials.gov Identifier: NCT03636477) were presented at the American Society of Clinical Oncology ASCO20 Virtual Scientific Program earlier this year.3
The data presented from 21 patients show a reasonable safety profile and evidence of some preliminary immune effect, such as slightly increased cytotoxic T-cell counts in the peripheral blood.
“The study is very well done and concluding it’s safe is a good result for a phase 1 study. I’m not sure it’s reasonable to ask for significant efficacy data at this point, but that’s the reason that they are doing the phase 2, which will give us a more robust idea of efficacy,” said Dr Venur.
“The first thing that they show is they can do it safely. They are injecting a viral vector with a gene activated along with a drug that can cause side effects. They were able to show it’s safe and that some people see benefit,” said Dr Peters.
The presentation also featured 2 case reports of patients who had partial responses on the combination therapy.
“One of the patients they showcase in the ASCO presentation had great response even up to week 36, which is very good for a patient with advanced GBM. These are early days, but it’s a promising approach,” said Dr Venur.
Despite a generally positive safety profile, there were still some concerns that two-thirds of the treated patients displayed CRS, although all but one patient had grade 2, not grade 3, CRS.
“We are always worried about this effect [CRS] when we are stimulating a nonspecific immune response,” said Dr Venur. “This may be a barrier for this approach going forward, but we are really managing these side effects better, and we’ve learned a lot about these from [chimeric antigen receptor T-cell] treatments, for example,” he added.
Interestingly, the current situation with the COVID-19 pandemic may provide new information about treating CRS, which may be translational to managing the condition in patients treated with chimeric antigen receptor T-cell (CAR-T) therapies.
“Given the situation with COVID-19 right now, where CRS is a significant concern, a lot of new research is going into CRS — and we are going to learn more about it and how to suppress it. It’s an exciting paradigm,” said Dr Peters. “We are currently good at managing it and we are getting better,” she added.
Another hurdle that the therapy will have to navigate is dexamethasone. Patients with glioblastoma are typically given dexamethasone to both control the symptoms of the tumor itself, such as brain swelling and edema, but also to control treatment side effects.