Clinical trial: IDH1 R132H peptide vaccine + avelumab (Germany)

A prior trial tested this vaccine (IDH1 R132H peptide vaccine) for gliomas with this IDH1 mutation.  The current trial is testing vaccine alone versus avelumab (PD-L1 inhibitor) alone versus combined vaccine + avelumab.

It is recruiting first recurrent gliomas of grade 2-4 with the IDH1 R132H mutation.

Open in Heidelberg and Mannheim Germany, and will also be open at several other centres in Germany.

https://clinicaltrials.gov/ct2/show/NCT03893903

Neo-adjuvant (before surgery) pembrolizumab

Neoadjuvant anti-PD-1 immunotherapy promotes a survival benefit with intratumoral and systemic immune responses in recurrent glioblastoma

http://sci-hub.tw/https://www.nature.com/articles/s41591-018-0337-7

This was a small, randomized trial for recurrent GBM at first or second relapse, who were candidates for surgical debulking and were on steroid doses less than 4 mg per day of dexamethasone or equivalent.  There were 16 patients in each arm. One arm (neoadjuvant) received pembrolizumab (Keytruda) 14 days before surgery, and further doses of pembrolizumab after recovery from surgery. The second arm (adjuvant) received pembrolizumab only after surgery.

The survival advantage of neoadjuvant pembrolizumab was statistically significant (hazard ratio = 0.39, P = 0.04).  Note that it's more difficult to achieve statistical significance in a smaller trial versus a larger one.  Patients in each arm were well-matched for typical prognostic features.

In light of the positive results of this trial, "we intend to expand the current study and pursue further clinical trials with neoadjuvant combination immunotherapeutics."

Should we get the NGS done? If yes, from where?

Hi folks/Stephen,

Needed a bit of help from you all. My mom is a GBM patient who was diagnosed in Sep 2017. Her cancer is IDH1/2 -ve, methylated and 1p/19q codeletion negative, this is the information that we gauged from the initial gene testing that was done by our hospital post surgery. We are now considering a next generation gene sequencing test done, and I had the following questions on the same:

1. How helpful has the gene sequencing report been for you so far, if you have got one done? What questions should I look at getting answered from this test?

2. Since there is very little tumor tissue that we all have, which is the best place to get the gene sequencing done from? I currently have read and spoken to OncoDNA, StrandAdvantage, RGCC Greece and FoundationOne so far. Which one would you recommend, and why? The recommendation could be different from the mentioned five too.

I read the following doc shared by Stephen in the Brain Tumor library too, but I'm not quite able to figure out on which test is a more appropriate one for what kind of patient. 

https://docs.google.com/spreadsheets/d/1653spmu9DkVCKX16G0_ZUlsTuJOx_Ln2qVysJJI-uoU/edit#gid=0

There are so many genes written in all of them, that it's hard for me to be able to compare and make an informed call :/

Want to know if the gene testing will be of help in further treatment, and the drugs/supplements that we should use for her in the near future.

Her current status

1. Her MRI three months back showed no growth, but had choline elevation at two parts where there was tumor resection. We have her next MRI in about a week from now.

2. She will do her remaining chemotherapy cycles with Temozolomide+Lomustine, her cancer being methylated.

She currently is on ketogenic diet and lot of naturopathic supplements suggested by Nutrition Solutions. 

My plan going forward

After my mom is done with the chemotherapy, I plan to get her immunotherapy (Dendritic cell therapy) done.  Want to know if the gene sequencing will be an add on in this plan.

Blood-brain barrier and immune checkpoint inhibitors

Blood-brain barrier and immune checkpoint inhibitors

My partner has a recurrent and unoperable glioblastoma.
He is considering a therapy with immune checkpoint inhibitors (e.g. pembrolizumab or atezolizumab) as his tumor has extremely high mutation burden. Some doctors are in favour but some are not convinced and say that it won't work because of blood brain barrier (BBB).
Is there any research showing immune checkpoint inhibitors don't cross BBB?

Immunotheraphy combo

Do you have any experience or thoughts about this study?
http://www.practiceupdate.com/c/57122/67/12/?elsca1=emc_enews_weekinreview&elsca2=email&elsca3=practiceupdate_braincancer&elsca4=braincancer&elsca5=newsletter&rid=MjMxMDE2NzMzNjcyS0&lid=10332481

Has anyone tried this combo?
Best wishes to all
Brainbutton

Brain Research Institute

I found this link on ABTA and thought it was helpful. 

http://www.cancerresearch.org/cancer-immunotherapy/impacting-all-cancers/brain-cancer