The phase 1 MAGIC-G1 trial is investigating delivery of MTX110, a new formulation of panobinostat (drug approved to treat multiple myeloma), directly to the tumor site via catheter in recurrent glioblastoma (GBM). Of the first 4 patients treated, two have died (one at 12 and one at 13 months after treatment). The third patient had 6 months progression-free survival (PFS) and is at 13 months overall survival (OS) so far. The fourth patient has not yet had progression and is at 12 months PFS and OS.

While this is a very small, early-stage study, the outcomes so far compare favorably to historic survival rates for recurrent GBM, and the drug appears to have a manageable safety profile. We'll be keeping an eye on this one.

This University of Miami study used daily non-contrast MRIs with a ViewRay MRI-linear accelerator (MR-linac) to deliver radiation therapy to glioblastoma (GBM) patients. The results suggest this technique can be used for adaptive radiotherapy, where radiation oncologists can rapidly modify treatment plans based on observed tumor changes or surgical cavity shrinkage. While this study used non-contrast MRIs, this method could also be used to guide decisions on when a mid-radiation contrast MRI might be warranted for treatment adjustments. Only a few medical centers across the country offer this radiation approach, but we hope to see broader adoption and availability in coming years.     

Patients newly diagnosed with a brain tumor often seek out stories from others who have survived and thrived despite having the same diagnosis. These stories are crucial for giving hope and motivation to patients, caregivers and families. The Musella Foundation is looking for brain tumor Survivor Stories for potential inclusion on our Survivor Stories webpage, in our Brain Tumor Guide for the Newly Diagnosed (focused on high-grade brain tumors), and/or in our forthcoming Low Grade Brain Tumor Guide (focused on low-grade brain tumors). 

If you would like to share your brain tumor Survivor Story, please send an email to vanessa@virtualtrials.org.

There is substantial interest in the ketogenic diet as a potential complementary approach to standard treatment for glioblastoma. While more research is needed, this recent meta-analysis provides a succinct overview of the available evidence to date.   

The annual European Association of Neuro-Oncology conference (EANO 2024) is coming up in a few weeks, and one of the presentations will share data from the Phase 0/1 study of mycophenolate mofetil (MMF) in newly diagnosed and recurrent glioblastoma (GBM). MMF inhibits an enzyme required for purine metabolism in GBM cells. The study, although small, showed effective target engagement and inhibition of purine synthesis. Interim median overall survival was 15.6 in the recurrent GBM arm of the study and was not yet reached in the newly diagnosed arm. Based on the study results, the investigators have identified a recommended dose for a future Phase 2 trial.

We covered an earlier iteration of this research in our SNO 2023 highlights, and the full paper is now published in the journal Nature Medicine. Researchers at ETH Zurich used a novel screening platform to test 130 repurposed neuroactive drugs on fresh glioblastoma (GBM) tumor samples. The screening identified the antidepressant vortioxetine as a promising drug candidate for GBM, and follow-up preclinical mouse testing corroborated the finding. The researchers are now preparing two clinical trials to see if vortioxetine alongside standard of care can help improve survival for GBM patients. It's worth noting that vortioxetine outperformed fluoxetine (Prozac) in the screening platform; however, human testing of vortioxetine is still needed to find appropriate dosing and to confirm safety and efficacy in GBM patients. Published real world evidence has shown that Prozac may extend survival in GBM patients, and we're eager to see if vortioxetine can do the same.

Pinpoint Patient Recruiting, a market research recruitment company, is searching for people who have been diagnosed with GBM, or people who are currently caring for a loved one with GBM, to participate in a 30-minute online survey about their experiences with this condition and their opinions on treatments and care.

If you or your loved one were diagnosed with GBM in the past 24 months, you may be eligible to participate. Those who qualify for and complete the survey will receive $75 as a thank you. They will also make a donation to the Musella Foundation!  All information and responses will remain confidential. Participants must be 18 or older and live in the U.S.

To see if you qualify for the study or to get more information, please visit pinpointpatientrecruiting.com/gbm-survey or contact Jenny Fowle at jenny@pinpointpatientrecruiting.com.

* Please be sure to mention Musella Foundation when asked how you heard about the survey!

Researchers at the University of Miami are using whole-brain MR-spectroscopy (WB-MRS) and a new machine learning technique to predict brain tumor recurrence much sooner than detection on traditional MRI scans. WB-MRS provides detailed metabolic information across the entire brain, allowing for a more comprehensive view of tumor activity. While this was only a small pilot study, we hope to see broader application and validation of WB-MRS predictive models going forward. 

This is a UK story, but we see this happen to patients every day in the US. Clinical trial inclusion/exclusion criteria are extremely rigid, and only a small percentage of brain tumor patients are able to qualify for the most promising trials. It's heartbreaking, and it's exactly why we need everyone's support for the Promising Pathway Act. 

From our friends at the George Bartol Memorial Scholarship Fund:

Hello everyone! We are excited to honor our father for the 20th year in granting scholarships! Applications for the George Bartol Memorial Scholarship Fund are due by October 1, 2024. Winners will each receive $3k towards their educational expenses in 2025. Please reach out for an application if you meet the criteria below!

Criteria to apply:
1. Lost a parent or have a parent battling brain cancer. (Primary in origin, not metastatic.)
2. Degree seeking student at any US college or university.
3. 2.5 GPA or better
4. 23 years of age or less

*** Applications are due no later than October 1, 2024. Please send a message to the George Bartol Memorial Scholarship Fund on Facebook to request an application. 

Great news. In the Phase 3 INDIGO trial, this targeted drug more than doubled progression-free survival and delayed the need for radiation and chemotherapy for patients with Grade 2 IDH-mutant glioma following surgery. It will likely become standard of care first-line therapy for Grade 2 IDH-mutant glioma. We don't yet know whether it will be helpful for high-grade gliomas (HGG) harboring an IDH mutation, but it's worth a discussion. Many HGG patients with IDH mutations are already trying off-label IDH inhibitors (e.g., ivosidenib/Tibsovo).

We're excited to see this long-awaited publication. The CeGat clinic, based in Tubingen, Germany, provides advanced genetic testing of tumor samples and uses it to make personalized peptide vaccines for glioblastoma (GBM) patients. These vaccines were not tested in a formal trial setting, but the real-world results look promising. From Oct 2015 to Aug 2023, 173 GBM patients were treated, with a median of 19 personalized peptides included per vaccine. Seventy patients were treated before tumor progression (newly diagnosed) and 103 were treated after progression (recurrent). The vaccines were well tolerated, and many patients developed durable immune responses. Median overall survival (OS) for the newly diagnosed cohort had not been reached at the time of data cutoff, and median OS was 23.8 months for the recurrent cohort. Median on-treatment survival from initiation of vaccine treatment was 28.9 months for the newly diagnosed versus only 9.8 months for recurrent patients. Importantly, significantly prolonged survival was observed for patients who had multiple vaccine-induced T-cell responses (53 months) compared to those with no/low induced responses (27 months).

As acknowledged by the study authors, there are factors that may have biased the data, such as the time required for vaccine production (median time from diagnosis to first vaccination was 10.3 months; range 3-54 months), patients' socio-economic status (the cost of treatment, as well as travel for treatment, was substantial), and the varied additional treatments patients may have received (additional therapeutic strategies were applied at the discretion of patients' primary treating physicians). Nevertheless, the connection between vaccine-induced T-cell response and prolonged survival is cause for hope, and we look forward to seeing more data on personalized peptide vaccines, especially in combination with other treatment strategies!

Medicaid fee-for-service patients in New York are currently being denied access to Tumor Treating Fields (TTFields) therapy. TTFields is recognized by the National Comprehensive Cancer Network (NCCN) guidelines as standard of care for glioblastoma (GBM) and is covered by Medicare and more private insurance carriers. Yet, the New York State Department of Health continues to deny access to patients who receive fee-for-service care on Medicaid. 

If you're a New York resident with a connection to brain cancer, please help us advocate for Medicaid coverage of TTFields. (Click HERE for more info.)

We have, again, run out of funds for this life saving program. The program is dependent upon donations earmarked specifically for this purpose. If you'd like to contribute, please go to virtualtrials.org/donate and select 'Copayment Assistance Fund' when making your donation. We'll let everyone know when we have enough money to reopen the program.

Our Copayment Assistance program is nearly out of funding and will probably close to new patients in a few days. Of course, we will continue to pay claims for those already approved, but we will be unable to approve new or renewal claims. 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 the donation!    

Researchers at USC developed a machine learning method to identify specific molecules, called cell fate determinants, that can convert GBM cells into cells that function similarly to dendritic cells (DCs), which are important for activating an anti-tumor immune response. The machine learning technique can analyze tens of thousands of genes and millions of gene connections within GBM cells to find those that can be transformed using CFDs. Once the GBM cells are treated with the CFDs, they acquire characteristics and functions of natural dendritic cells, including the ability to capture and present antigens, which are pieces of the tumor that T cells need to recognize in order to mount an attack. In mouse models, this new approach led to a reduction in tumor growth and improved survival rates. When combined with other immunotherapies, the treatment worked even better. While further development is needed and human trials are still likely a few years away, this is an exciting and innovative approach.     

Earlier this month, we announced a $50,000 grant to DNKO LLC for preclinical research on a treatment using heat sensitive liposomes combined with LITT for targeted drug delivery. We now have a brief webinar available on the project, as well as a donation fund set up to help get this treatment into human trials.      

This trial was discussed during our May Brain Tumor Awareness Month Webinar series: see here. The treatment used to be called PVSRIPO, but it's now called Lerapolturev. The trial is now recruiting, with the aim of enrolling up to 80 patients with supratentorial recurrent glioblastoma who are eligible for maximal safe resection for their recurrence. 

This preclinical study used an interesting combination of immunotherapies (fc-enhanced anti-ctla-4 and anti-pd-1), chemotherapy (doxorubicin), and specialized drug delivery (pulsed ultrasound and microbubbles). It was highly effective in murine models, achieving a 90% cure rate as well as immunological memory. There is a Phase 2 clinical trial at Northwestern University testing this combination in newly diagnosed glioblastoma.

From our friends at Roon!
As many of you know, the Musella foundation has partnered with the Roon team to help create a wonderful online resource for those navigating glioblastoma. The app has top experts (you can see them all here https://www.roon.com/gbm/experts  from across the country answering all the questions that come up during the journey of GBM. The answers are provided via short form video and easy to consume. All the content is curated and contextualized into the journey of the disease. The newest features include AI to help you find the information you need most easily. On their home screen, you can ask the system any question you have, and it will respond with an answer sourced from the experts on Roon. From there, you can find and explore the videos.