News in Research on Glioblastoma in the Fourth Two-Months 2023

Punctual as usual, this is the twenty-second article of the project which aims to collect periodically (every two months) the latest research on possible treatments for glioblastoma multiforme.
Below are the news that we considered most significant. As with the previous articles in the series, each news item will be preceded by the original title with a link to the source and followed by a brief comment. The criterion with which news items are chosen is always to generally include only news relating to research in the clinical phase, unless the potential of research for the treatment of glioblastoma is truly remarkable.

Prognostic survival biomarkers of tumor-fused dendritic cell vaccine therapy in patients with newly diagnosed glioblastoma
The results of this study are interesting. Even in patients with wild-type IDH glioblastoma and unmethylated MGMT, which typically indicates a worse prognosis, the five-year survival rate reached an encouraging 33%. However, this study has significant potential because it aims to understand which type of patient these therapies are effective for. Older age and pre- and postoperative Karnofsky score are significantly related to survival. Low expression of HLA-A and lack of CCDC88A, KRT4, TACC2 and TONSL mutations in cancer cells correlate with better prognosis. It’s important to note that these findings are based on early-stage research with a small number of patients, so caution should be exercised before drawing firm conclusions. However, these studies are very important because in the end they provide us with a further step in understanding how to personalize therapies.

IL4R-Targeting Toxin MDNA55 Yields Promising OS in Recurrent Glioblastoma
Remarkable results obtained with a single injection of this toxin on patients with recurrent inoperable glioblastoma. Interleukin receptor 4 (IL4R) targeting the toxin MDNA55 achieved tolerable tumor control and extended survival in a group of patients with glioblastoma, wild-type, inoperable, recurrent IDH. In the population considered (n = 47), the median overall survival (OS) was 10.2 months. The 12-month OS rates were 43%.

NOX-A12 Plus Radiotherapy and Bevacizumab Produces Responses in Previously Untreated Glioblastoma
These are the first results on a small number of patients, but the results are very good. Therapy consists of the addition of CXCL12 inhibitor (NOX-A12) to standard of care (SOC) which consists of radiotherapy and bevacizumab (Avastin). Newly diagnosed patients with unmethylated MGMT who had not undergone complete resection and therefore had only a biopsy or debulking (partial excision) were considered. This is the worst subgroup of glioblastoma and alas it was also the group Emanuele found himself in. Of the 6 patients involved, 5 of 6 are alive at month 15, 1 had a complete response, 2 had a 99% response, and 2 had a duration partial response! It is very rare to see a complete response or a 99% response of patients with unmethylated MGMT. The study is still ongoing and is worth serious consideration.

United States Food and Drug Administration (FDA) Authorizes Phase 2 Study of DB107 In Promising Turn-Around of Targeted Treatment to Treat Newly Diagnosed High Grade Glioma
This study is also very intelligent and makes us understand the tendency to make therapies more targeted. They looked at failed studies where some patients had good results and understand why they failed and which patients benefited. Then perform the trial only on those patients who are expected to have a good outcome. They’re going to take Toca511 and TocaFC (now called DB107) and start a trial just for people with the correct biomarker. The original tests of the Toca511 looked very good. However, the randomized phase 3 trial failed. Now they know which biomarkers have been successful. So the study had not helped the average patient, but a long queue of people who had this biomarker! Here too we are moving towards personalized therapy.

Perlmutter Cancer Center Enrolls First Participant in Study of Noninvasive Treatment of Glioblastoma
This is another trial among several competing for sonodynamic therapy. In practice, 5-ALA is injected which is deposited on the tumor cells and only on them. Then the ultrasounds are activated which make those cells vibrate until they are killed. It is a very interesting non-invasive and targeted therapy. It is to be hoped that these clinical trials will be successful and become another building block to be used to defeat glioblastoma.

Northwest Biotherapeutics Announces Completion of Prerequisites, and Plans for Submission of Marketing Authorization Application
This is news I’ve been waiting for for a long time. Northwest Bio has announced plans to apply for approval of DCVax within the next month. The approval process is expected to take approximately 150 business days. After various announcements and criticisms on the way to collect data from the phase 3 trial, all doubts have finally been resolved and the contested data recalculated. DCVax is a dendritic cell-based vaccine customized to a patient’s specific tumor. A sample of the tumor is needed to create the vaccine. Results from a large Phase 3 study have been very promising, and preliminary data from ongoing trials involving combination therapies look even better. Once approved, the therapy will become part of the new standard of care in the US. When this therapy will become standard of care in Europe and Italy we don’t know yet but I personally hope soon. The cost of the therapy in compassionate use which for now can only be done in the UK is truly considerable and is difficult to apply as often there is no fresh sample of the tumor from which to develop the vaccine.

That’s all for this issue on research news. Remember to register and enter your patient profile in Glioblastoma Navigator, the system is active and two video tutorials have been prepared. A Video Tutorial for Pazients and Caregivers and a Video Tutorial for Specialists (Doctors and Researchers).

If the number of subscribers does not soon reach a thousand, we will have to consider the project failed and therefore frustrate all the efforts used up to now to develop it. In this article I take stock of the project and ask for feedback to understand how to reach more patients. I ask you to read it and send me useful suggestions.
Good luck and sincere wishes to all those who are fighting glioblastoma and their loved ones!