Impressive results for a phase 1 trial.  The link to the journal article is in the press release.

 Thyis may be a new way to detect recrrences sooner!

 This is a very interesting drug. It is a smart bomb. It seeks out IL13Ra2 which is a cell surface protein present on many types of cancer cells (including Glioblastomas, and DIPG), and rarely found on normal cells. It carries along a pseudomonas exotoxin that kills the cells that the drug attaches to. The net effect is that it kills tumor cells without harming the normal cells.  The Musella Foundation has given a few grants to support the creation of this drug over the last 11 years and I am so happy to see it has received orphan designation. That will make it easier and cheaper to  bring it to patients.

 One of the key findings is onky 42% of the elderly patients in the USA with Glioblastom used any chemotherapy compared to 63% of younger people. Same problem with radiation and surgery, all 3 of which were shown to increase survival time if used.   They found the average survival time was only 9.1 months. We need to figure out why these people did not receive treatment.  Cost may be a factor.  The first Temodar prescription usually costs in the neighborhood of $8,000 with a medicare copayment of about $1,000. Many people refuse to buy the Temodar due to the cost. The manufacturer of Temodar closed their assistance program a long time ago and right now we - the Musella Foundation - are the only copayment assistance program open that can help Medicare patients with their copayment for Temodar (and Optune and Avastin). (Others open and close but none are open now).  We helped over 1,500 patients pay for the medications they need. I am sure this has helped these people live longer. Having said that, we need to change the laws so people who have health insurance do not have to go without medicines due to their cost.

This can be practice changing.  We previously reported that Temozolomide did not help patients with Glioblastoma that have unmethylated MGMT and the Wild Type IDK. This confirms it, and in the opinion of the authors, makes it Ok to not use Temozolomide on patients in this group, and try something else.  We have always been afraid of trying this because there was a small "tail" of survivors in the trials of patients with unmethylated MGMT who did do well with Temozolomide.  This article explains that the old test was not specific enough, and says they now break down the MGMT result into 3 groups, highly methylated, where Temozolomide has a good chance of helping, low (truly) unmethylated which has no chance of Temozolomide helping, and the intermediate range where there may be a small benefit. They say that those in the intermediate group were labelled as unmethylated and they account for those responders in the old trials.

The  Bridge to a Cure Foundation raises money to fund pediatric cancer research and is trying to unite the organizations working on pediatric cancer to work together to speed up the pace of research.  By joining their board, I will help them work with the pediatric brain cancer groups!   Of course, I will still run the Musella Foundation and participate in all of the other collaborations we are in. This will help raise the funds we need to implement some of the great ideas these collaborations have but were unable to fund!

 Finally good news for those of us with a weight problem.  The study is too small to prove anything but they found that obese individual had a 5 month increase in median survival compared to non obese patients. It would be interesting to check this on other databases and see if it is real.  If it is, then we have to account for BMI in clinical trials as the 5 month difference is more than the difference needed to get a drug approved. 

 This is an important study.. they looked at the mitochondria of the tumor cells, and found differences among some of the tumors that may open an Achilles heel. This subgroup might be treatable with existing approved drugs (such as Metformin).  The Musella Foundation recently awarded a grant to a different set of researchers to study this in depth.

 This is one of my favorite trials... PVSRIPO + Keytruda makes a lot of sense. The PVSRIPO is injected into the tumor and kills tumor cells.  The Keytruda ramps up the immune system so that it learns from these destroyed tumor cells and seeks out and kills tumor cells anywhere else in the brain (and maybe the entire body).  PVSRIPO by itself is a good treatment. For recurrent Glioblastoma, they reported a 3 year survival rate of 21% compared to historical controls of about 4%.  Hopefully adding Keytruda will increase that significantly.  Keytruda by itself did not really work out well with Glioblastoma, because it only revs up the immune system and there needs to be something there for the immune system to see.   The PVSRIPO kills the cells, making them into a better target for the immune system.

Disclaimer: I am on the patient advisory board of the Brain Tumor Center at Duke.

Interesting study.  They found that people who had a T. gondii infection, as determined by having antibodies against the parasite were more likely to develop a brain tumor. More research needs to be done to repeat this experiment in different groups of patients, and to  see if the parasite can really cause a tumor and / or influences the growth of the tumor.  There are other conflicting studies that did not show the association, but this one seems the best designed.

 I really like this trial.  They may have figured out why the vaccine wasn't working that well, and found a way around it. They tested it in dogs who had naturally occurring tumors and it worked pretty well. Now they are doing a clinical trial of the vaccine plus the CD200 checkpoint inhibitor in humans with recurrent glioblastoma . I will be watching this closely and wish them luck.  For details on the trial, go to https://clinicaltrials.gov/ct2/show/NCT04642937

 Hopefully this will speed up the FDA approval process for Onc-201. This drug should have been approved last year. 

 The GBM Agile trial is the next generation of clinical trials. It is an adaptive design which allows flexibility to change as circumstances dictate instead of the rigidity of the old style trials.  

Very exciting news.  As I mentioned in a few previous posts (such as https://virtualtrials.org/newsarticle.cfm?item=6750) , the G47 Delta virus did remarkably well in a phase 2 trial for recurrent or residual Glioblastoma.  They reported a 1 year survival rate of 92% compared to historical controls of 15%.  This article says they applied for the Japanese equivalent of our FDA approval for it last month.   So at least in Japan, there will hopefully be a new, effective  Glioblastoma treatment soon. We have to work on getting it here in the USA.

 Leptomeningeal spread is a serious complication.  Left untreated, average survival is only 2 months.  The article talks about a few treatments but there is an interesting clinical trial going on specifically for patients with leptomeningeal  spread: Brain Tumor-Specific Immune Cells (IL13Ralpha2-CAR T Cells) for the Treatment of Leptomeningeal Glioblastoma, Ependymoma, or Medulloblastoma  It is too early to tell how good this works, but the alternatives do not seem that good either. Car-T cells have worked miracles in other cancers. This is a new type of Car-T cell treatment that hopefully will work for brain tumors!  They picked the absolute worst situation to test it in - so if it does work we should know quickly. Unlike most immunotherapies, Car-T cells have the possibility (at least in other cancers) of working quickly. 
Disclaimer: The company running the trial, Mustang Bio, is a sponsor of the Musella Foundation.  

 This article suggests it is safe to freeze your eggs before treatment for a brain tumor, then implant them after the treatment, without risk of spreading the tumor. 

  If you think you may need assistance paying for these covered treatments, apply. Do not feel awkward asking for help. One of our main objectives is to help reduce the stress in your life! The other one is to speed up the search for the cure!

 Canada finally approved Gleolan.  The USA FDA approved it here in the USA about 3 years ago.  Gleolan is a dye used at the time of surgery to allow the surgeon to see any remaining tumor cells. It has been shown to increase the chances of a complete resection, which increases the progression free survival time.    

This doesn't mean that Opdivo (Nivolumab) doesn't help Glioblastomas. They just tried to use it incorrectly.  Opdivo is a checkpoint inhibitor. It takes the brakes off of the immune response to help your body fight the tumor.  But there has to be an immune response present for it to work.   Unfortunately Glioblastomas are not a "hot" tumor and by itself doesn't really generate enough of an immune response that Opdivo can enhance.  Something needs to be done to the tumor to initiate that immune response, then use Opdivo to enhance it.  One possibility is starting Opdivo before the surgery when there are a larger number of tumor cells present and the act of the surgery itself triggers an immune response which Opdivo can enhance.  Or during radiation when cell death causes an immune response.  In this trial they waited until the radiation was over and the immune response slowed before starting Opdivo.  

Another possibility is to use Optune at the same time as Opdivo. Optune triggers an immune response as it kills the tumor cells. Vaccines may do the same.  This is why we need the Promising Pathway Act that I proposed.   We need to be able to try different combinations and see results quickly.