As we close out the year, we're proud to share our Musella Foundation 2024 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! 

Under our current system, there is a 4.7 year gap between when a medical device gets FDA approval and when it gets coverage by Medicare. This proposed bill would close this "Valley of Death" lag for Medicare beneficiaries. If enacted, this bipartisan legislation will help ensure that American seniors are granted faster access to innovative medical devices and diagnostics. For brain cancer patients, there are at least 3 medical devices in development that may be eligible for this once approved by the FDA. We do not have 4 extra years to wait for Medicare to allow us access to these treatments! To advocate in favor of this bill, please click here!

The Musella Foundation helped fund this research looking at how different treatment options affect length of survival for children with DIPG. Children with DIPG who did not receive any treatment had a median survival of just 3 months. Children who had only radiation lived for a median of 10.4 months from diagnosis. Those treated with both radiation and chemotherapy had a median survival of 11.7 months. These numbers are horrific and show that new treatments are urgently and desperately needed. If the Promising Pathway Act was passed, we would have better treatments right now.

 Mark your calendars for December 18 at 7pm EST! We'll be hosting a webinar with Dr. Michael Schulder on sonodynamic therapy for high-grade gliomas. 

The Musella Foundation attended the Society for Neuro-Oncology (SNO) Annual Meeting this past week. We're working on a comprehensive summary of highlights which will be shared soon, but in the meantime, we wanted to call attention to an important abstract on a Phase 1 trial of 12 newly diagnosed glioblastoma patients treated with a personalized neoantigen vaccine alongside the standard of care, including tumor treating fields. The results are remarkable: 100% progression-free survival at six months, 67% 2-year survival, and 58% 3-year survival. However, one patient experienced serious adverse events which ultimately led to brain demyelination and death. We really hope to see continuation and expansion of this research, not only for the exciting survival results, but also to gain a better understanding of this potential safety concern for personalized neoantigen vaccines (i.e., unintended T-cell cross-reactivity, potentially contributing to brain demyelination in one patient).

Alpheus Medical has announced exciting results from their Phase 1/2 sonodynamic therapy (SDT) trial in recurrent or refractory high-grade glioma. The results were also presented at the SNO conference by Dr. Michael Schulder.

The trial combined low-intensity diffuse ultrasound with oral 5-aminolevulinic acid (5-ALA) in 12 patients across three cohorts, with escalating treatment durations. The treatments were delivered monthly for a minimum of four sessions, and a treatment duration of 120 minutes was established after dose escalation.

Results showed significantly extended median overall survival (OS) to 15.7 months and progression-free survival (PFS) to 5.5 months, compared to historical data of approximately 6-8 months and 1.8 months, respectively. This is particularly impressive given that two patients were enrolled after multiple recurrences and seven patients had multifocal or multicentric disease. 

Alpheus plans to start a randomized, controlled trial at multiple centers across the U.S. in 2025. We did a webinar with Alpheus in early 2023, and we hope to host another updated one soon!
 

Orbus Therapeutics has now shared results from their global Phase 3 STELLAR trial, which tested a combination of eflornithine and lomustine in patients with recurrent anaplastic astrocytoma. Eflornithine is a drug that slows tumor growth by blocking ornithine decarboxylase, an enzyme that helps cancer cells grow and divide.

The primary efficacy endpoint for the study, overall survival in the intent-to-treat population of 343 patients, did not achieve statistical significance. However, the company noted promising and clinically meaningful improvement for a subset of 194 patients in the study who had recurrent grade 3 IDH mutant astrocytoma. In this subset, patients receiving the combination therapy had a median OS of 34.9 months, compared to 23.5 months with lomustine alone. Median PFS was 15.8 months versus 7.2 months with lomustine alone. The treatment was generally well-tolerated although, consistent with prior eflornithine studies, there were some Grade 3+ adverse events related to myelosuppression and hearing impairment.

Congratulations to our President, Al Musella, for joining the board of IQ-AI! The Musella Foundation has been helping Imaging Biometrics, a subsidiary of IQ-AI, fund and run an expanded access program for their glioblastoma drug candidate, oral gallium maltolate. Additionally, we are starting a new project using Imaging Biometrics' unique software, which creates Fractional Tumor Burden Maps from MRI scan data, to help monitor glioblastoma patients starting Optune so we can tell earlier if Optune is working for that patient or not!  

The Musella Foundation Copayment Assistance program is now open to new patients as well as those seeking renewals of their grants. The program helps patients with high grade brain tumors pay for Temodar, Optune, Avastin, and Gleostine (and their generics). For details and to apply, visit braintumorcopays.org.

UNC Lineberger is the third treatment center to complete site activation for the Oral Gallium Maltolate Expanded Access Program! The program is also currently available at Providence Mission Viejo (California) with Dr. Santosh Kesari and at Northwell Health (New York) with Dr. John Boockvar. If you are interested in accessing this program but do not live near one of the 3 open centers, you can ask your doctor to contact eap@imagingbiometrics.com for information on how to join the program. 

These are Al Musella's personal thoughts on what he would do if diagnosed with a Glioblastoma. The document is updated periodically, and this latest update was completed on 10/24/24.

NuvOx Pharma is a company developing a new drug called NanO2. They have a currently recruiting Phase 2b trial called RESTORE, which is testing NanO2 together with standard of care for newly diagnosed glioblastoma. NanO2 was developed based on technology similar to ultrasound contrast agents, but modified to carry and deliver oxygen. The drug is meant to reverse tumor hypoxia, a condition that hinders the effectiveness of radiation and chemotherapy. The study investigators recently published two new journal articles, one to explain how NanO2 works and the other to describe the design and rationale for the Phase 2b clinical trial. 

In their quarterly financial report, Novocure announced that the FDA granted Breakthrough Device designation for the use of Tumor Treating Fields therapy for brain metastases from non-small cell lung cancer. The Breakthrough Device designation is a special status granted to innovative medical devices that have the potential to more effectively treat life-threatening or irreversibly debilitating conditions and allows for expedited development and review process so these devices can potentially reach patients faster.  

This is really interesting research on improving the durability of treatment response from Tumor Treating Fields (TTF). This preclinical study found two key factors related to TTFields treatment resistance: a receptor called EP3 and a protein called ZNF488. These proteins work together to help cancer stem cells survive and grow, making them resistant to TTFields. When researchers blocked these proteins, the cancer cells became sensitive to TTFields again, and their ability to grow and form tumors was reduced. Blocking EP3 also helped stop resistance before it started. This discovery suggests that targeting EP3 and ZNF488 could help overcome resistance to TTFields, not only in GBM but potentially in other cancers as well.

This study looked at financial toxicity (FT) in glioblastoma patients who underwent craniotomy from 2020 to 2022 at a single center. Of the 74 patients studied, nearly half experienced FT, with an average medical ‘bad debt’ of $7,476. FT was more common in younger patients, those with longer hospital stays, and those who had subtotal rather than total tumor resections. This is a heartbreaking problem, and it’s why the Musella Foundation started our copayment assistance program.  

This is a great review highlighting the mechanisms of action and expanding applications of Tumor Treating Fields (TTFields) therapy, as well as promising ongoing research exploring the use of TTFields combined with immunotherapy and radiotherapy. 

This was a phase 2 study of lutetium-177 (177Lu) dotatate in patients with surgery- and radiation-refractory meningioma. 177Lu-dotatate is a targeted treatment that uses a radioactive compound to deliver radiation directly to tumor cells.

The single-arm trial enrolled 20 patients with WHO grade 2/3 meningiomas who had measurable disease with at least 15% tumor growth over 6 months and a Krenning score ≥ 2. The study met its primary endpoint; the 6-month progression-free survival (PFS) rate of 77.8% was significantly greater than the 26% historical benchmark. Overall median PFS was 11.5 months, and the 2-year PFS rate was 26.7%. The 1-year overall survival (OS) rate was 88.9%, and the 2-year OS rate was 63.8%. Median OS was 27.8 months.

The treatment was well tolerated, with no grade 4 or 5 adverse events attributed to the treatment. The most common grade 3 hematologic adverse event was low lymphocyte count.

There is currently no standard of care established for surgery- and radiation-refractory meningioma, so this study is a promising step forward. 

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.