Good news from IN8bio! They recently announced positive trends from their Phase 1/2 trial of gamma-delta T cell therapy in newly diagnosed glioblastoma. Patients treated with repeated doses had a median progression-free survival of 13 months, nearly double that seen with standard of care. Median overall survival has not been reached, but it exceeds 17 months so far. Several treated patients remain progression-free beyond two years, and the therapy has been well tolerated, with no serious treatment-related toxicities reported. 

GammaTile is a small implant placed in the brain at the time of resection surgery that delivers radiation right away instead of waiting weeks for standard post-surgery radiation. It was first cleared by the FDA in 2018 for both newly diagnosed and recurrent glioblastoma (GBM) and has been used in patients for several years. Now, GT Medical Technologies has started enrolling patients in the BRIDGES trial, a large randomized study to see whether GammaTile helps people with newly diagnosed GBM live longer compared with the current standard of care radiation. 

Researchers at the University of Michigan developed a machine-learning based “digital twin” program that maps how individual brain tumors use nutrients. Published in Cell Metabolism, the approach integrates patient blood data, tumor genetics, and limited metabolic measurements taken during surgery, including isotope tracing, to predict tumor-specific metabolic dependencies. Some tumors rely on particular amino acids or pathways and may be slowed by dietary changes or drugs, while others can bypass these restrictions.

The researchers validated the model using data from glioma patients who received labeled glucose during surgery and confirmed predictions in mouse models. The digital twin accurately identified which tumors would respond to the drug mycophenolate mofetil, while also distinguishing tumors that could evade the drug by using alternative “salvage” pathways to obtain DNA-building materials.

This is exciting work, and we hope to see further development and validation!

Researchers at Memorial Sloan Kettering found that PGBD5, a gene known to drive pediatric brain cancers by cutting and rearranging DNA, also plays an essential role in normal brain development. The study shows that PGBD5 deliberately creates DNA breaks in developing neurons that are precisely repaired to support proper neuron formation and function. This makes PGBD5 a rare “double-edged” gene whose beneficial developmental role can, when misregulated, lead to childhood cancers and neurodevelopmental disorders.

This important finding will hopefully lead to future development of therapies that can block PGBD5’s cancer-causing activity while preserving its normal role in brain development, potentially leading to safer treatments for pediatric brain tumors.

Our copay program is currently closed. We will reopen again when we are able to raise more funds. Of course, we will continue to pay claims for those who have an active grant. This program is funded entirely by donations earmarked for this purpose; if you'd like to make a donation towards this program, go to virtualtrials.org/donate and select 'Co-payment Assistance Fund' when you make a donation! 

A recording of our webinar with Dr. Vijay Agarwal on sonodynamic therapy is now available on our website. If you or a loved one is newly diagnosed with glioblastoma and choosing not to wear Tumor Treating Fields (Optune), the trial discussed near the end of this webinar is worth considering. There are 8 trial sites in the United States and two trial sites in Germany. 

This is an interesting recent study suggesting that IDH-mutant gliomas may arise from glial progenitor cells that already carry the IDH mutation long before a tumor is visible on MRI. Rather than starting as a discrete mass, the disease appears to begin quietly within normal-appearing brain tissue, particularly in progenitor-rich regions of the cerebral cortex, and evolve over many years. The tumor that is eventually diagnosed may therefore reflect not the true point of origin, but the site where these early mutated cells replicate into a detectable mass. In contrast, IDH-wildtype gliomas are thought to originate from neural stem cells in the subventricular zone, a deeper brain region where new neurons are generated. Because these cells are inherently more proliferative and biologically unstable, IDH-wildtype tumors tend to declare themselves much more rapidly.

This new study strengthens the idea that different glioma subtypes arise from different cells of origin and follow distinct developmental paths. While compelling, the results will still need confirmation by other groups in larger cohorts. From a practical standpoint, the visible tumor remains the dominant and most aggressive population of cancer cells, but the hope is that future treatment strategies will combine aggressive local therapy at the tumor site with smarter surveillance and systemic treatments for preventing new growth from the deeper roots of the disease.  

This retrospective study from Japan analyzed 50 patients with newly diagnosed, IDH-wildtype glioblastoma (GBM), of whom 18 received temozolomide (TMZ) alone and 32 received TMZ plus bevacizumab as part of initial therapy; most patients in the TMZ-only group later received bevacizumab at first recurrence. Most patients in the study also received carmustine (aka BCNU or Gliadel) wafer implantation at surgery. Overall, adding bevacizumab upfront improved progression-free survival (PFS) but not overall survival, consistent with prior trials. When patients were stratified by tumor COX-2 expression, those with high COX-2 expression experienced significantly longer PFS and overall survival when bevacizumab was given upfront compared with TMZ alone (median PFS 22 v 8 months; median OS 25 vs 18 months), while no benefit was observed in patients with low COX-2 expression (median PFS 12 vs 15 months; median OS 24 vs 26 months). These results are biologically plausible and suggest that COX-2 may help identify a subset of newly diagnosed patients who benefit from early bevacizumab; however, given the retrospective design, small sample size, treatment crossover, use of BCNU wafers, and potential subjectivity of the immunohistochemistry biomarker scoring, these findings should be followed up with prospective validation. Also, the results may not apply to recurrent disease, where prior therapies can substantially alter tumor angiogenic biology.   

We are very excited to see this news about GB13! The Musella Foundation helped get initial research for this therapy started more than a decade ago, with grant funding provided in 2010 and 2012. Now, the company behind GB13, Targepeutics, is collaborating with Penn State College of Medicine, the Beat Childhood Cancer Research Consortium, and Four Diamonds to complete the final preclinical work needed to submit an FDA application and begin a Phase I/II clinical trial for children with DIPG.

GB13 is an investigational immunotoxin that uses a precision-targeting approach to attack tumor cells expressing IL13Ra2, a receptor commonly found on brain tumors but rarely on normal brain tissue. The preclinical evidence supporting GB13 is very strong, and the therapy received Rare Pediatric Disease Designation (RPDD) from the FDA last year. We hope to see this therapy advance to trial soon.

The FDA has approved a new safety warning for the birth control shot Depo-Provera, adding label language about a possible increased risk of meningioma. The update follows growing evidence, similar warnings already issued in Europe and Canada, and comes amid lawsuits alleging Pfizer failed to warn patients of the potential risk earlier. Depo-Provera is widely used in the U.S., making this an important development for patient awareness and informed decision-making.

Our brain tumor copayment assistance program is now open to new (and renewal) patients. This program can help cover the copay costs for: Optune, Avastin, Temodar, and Gleostine, as well as their generics. If you think you may need help, apply ASAP as the program often closes quickly. Go to braintumorcopays.org for details and to apply!

Recently published results from a multi-center phase 1/2 trial suggest that MRI-guided microbubble focused-ultrasound (MB-FUS) may improve outcomes when added to standard chemotherapy for newly diagnosed high-grade glioma. The study enrolled 34 newly diagnosed high-grade glioma patients between 2018 and 2022 (pre-2021 WHO reclassifications). Most of the tumors were IDH-wildtype, with a mix of MGMT-methylated and unmethylated cases. 

After surgery and standard chemoradiation, patients received monthly outpatient MB-FUS treatments given once at the start of each temozolomide cycle to temporarily open the blood–brain barrier in large, contoured regions. A median of four MB-FUS cycles were completed per patient (range 1-6), with some missed cycles due to COVID-19 disruptions. 

Despite the small size of the study, patients treated with MB-FUS and temozolomide had significantly longer progression-free survival (13.5 months) and overall survival (31.3 months) compared with a carefully matched external control group treated with temozolomide alone, and the survival benefit remained consistent across multiple sensitivity analyses designed to account for bias. Side effects related to the focused ultrasound were mostly mild, with no unexpected safety concerns. These early results provide strong support for larger, randomized trials to test this treatment strategy.

The STELLAR trial was a large, randomized multi-center study testing eflornithine plus lomustine versus lomustine alone in patients with recurrent anaplastic astrocytoma. At the time the study began in 2016, tumors from all enrolled patients were classified as grade 3 astrocytoma, but the 2021 WHO updates to tumor classifications later showed that the patients had different tumor types, including grade 3 and grade 4 IDH-mutant astrocytoma, and IDH-wildtype glioblastoma. When researchers analyzed results from the entire cohort, the combination treatment did not improve overall survival compared with lomustine alone. However, when they did a subset analysis specifically on patients with recurrent grade 3 astrocytoma that carried an IDH mutation, the results were significant. In this group, people who received the combination had a median survival of nearly 35 months, compared to 24 months with lomustine alone. Progression-free survival with the combination was almost 16 months, compared to roughly 7 months with lomustine alone. These meaningful survival gains have the potential to guide future clinical practice for treatment of recurrent grade 3 IDH-mutant astrocytoma. 

Join us next week on Monday, January 12th at 7pm EST for a webinar with Dr. Vijay Agarwal on "Sonodynamic Therapy: a Phase 2b Trial for Newly Diagnosed Glioblastoma." To join, visit virtualtrials.org/webinar.  

We are having a fundraiser event at Drive Shack in West Palm Beach, Florida on December 29th!  
Click HERE for details!

This was a very small early study done in India. They explored whether a combination of the supplements resveratrol and copper might affect glioblastoma biology. Ten patients received the supplements orally four times a day for roughly 11 days prior to resection surgery, and their tumor tissue was compared to samples from ten patients who did not. The treated tumors showed differences in several biomarkers linked to tumor aggressiveness, suggesting a possible biological effect on the tumor environment.

While these findings are interesting, there are important caveats. This was a small, short-term study that looked only at tumor tissue changes, not whether patients lived longer or felt better. Further research is needed to determine whether prolonged treatment with this combination can improve patient outcomes.

GE Healthcare, one of the largest MRI manufacturers in the US, is partnering with Imaging Biometrics (IB) to distribute advanced imaging software that can help doctors better distinguish brain tumor progression from treatment effects with "Fractional Tumor Burden" maps. This is encouraging news for the brain cancer community. We hope to see more widespread adoption of these tools that make it easier to monitor brain tumors and understand how they are responding to treatments. For a great webinar on Fractional Tumor Burden maps, click here. 

This new study from Japan provides further evidence in favor of adaptive radiation therapy (ART) for glioblastoma (GBM). The ART approach adjusts the radiation plan during treatment based on changes in the tumor or surgical cavity. In 59 GBM patients, ART was safe and showed promising outcomes: median overall survival was about 27 months, progression-free survival about 10 months, and serious radiation side effects were rare. While research on ART in brain cancer is still developing, it does provide hope that smarter, adaptable radiation plans could help patients live longer with fewer side effects.

Imvax reported top-line results from its randomized double-blind, placebo-controlled Phase 2b trial of IGV-001 in 99 patients with newly diagnosed (ndGBM). IGV-001 demonstrated a median overall survival (mOS) of 20.3 months, a 6.3 month improvement over placebo (14.0 months). Median follow-up was 22 months. The trial did not meet statistical significance for the endpoint of progression-free survival, but showed a very favorable profile with no drug-related serious adverse events. 

The study used 2:1 randomization across 19 U.S. sites, one of which was initiated by our Chief Scientific Advisor, Dr. Steven Brem! About 48 hours post-tumor resection, patients received biodiffusion chambers containing either personalized whole tumor-derived cell with an antisense oligonucleotide (IMV-001) or inactive solution (placebo); chambers were removed 48 hours later. All patients then received standard-of-care chemoradiation and maintenance temozolomide.

IGV-001 has Fast Track and Orphan Drug designations, and Imvax plans to meet with the FDA in the coming months to discuss the regulatory pathway. Given these significant results and the profound lack of promising options for GBM, we hope to see widescale patient access to this therapy in the near future. 

As we come to the end of the year, we're proud to share our Musella Foundation 2025 Highlights. Everything we do — funding research, expanding patient navigation services, providing vital educational resources, patient advocacy — can only be done with your support. Please consider making a year-end donation to help us continue driving progress, supporting patients and families, and bringing hope to the brain tumor community. Every dollar helps!