Expanded Access Protocol for PVS-RIPO (modified poliovirus) treatment for GBM

 This just posted on clinicaltrials.gov on Oct 23:

https://clinicaltrials.gov/ct2/show/NCT04599647

EAP for the Treatment of Glioblastoma With PVSRIPO

scroll down to bottom of the above link for contact info

Poliovirus (PVS-RIPO) phase 1 update

Thanks to Al Musella for bringing this to our attention.

https://virtualtrials.com/news3.cfm?item=6529  (Al's commentary)

https://www.nejm.org/doi/full/10.1056/NEJMoa1716435  (full study, HTML)

https://www.nejm.org/doi/pdf/10.1056/NEJMoa1716435   (PDF download)

Here, as in some other viral therapy/immune therapy trials, we're seeing a long tail of survivors, in this case 21% surviving to 2, 3, 4 and 5 years (all dose levels).  This is comparable to DNX-2401 phase 1 trial, where 20% survived at 3 years, or Toca 511 + FC (13% alive at 3 years, all dose levels).

The most intriguing part of the study is the observation that some of the patients had dramatic responses to chemotherapy (including lomustine) after treatment with the modified poliovirus.  The randomized phase 2 trial open now is testing poliovirus alone versus poliovirus + single course lomustine.

This trial is open and Duke, and soon to open at Massachusetts General, UCSF, and Boca Raton.

https://clinicaltrials.gov/ct2/show/NCT02986178

Updated statistics from Duke's modified poliovirus trial for recurrent GBM

• As of 2/01/2017, 52 pts were treated on study (1 each at DL1 and DL3, 7 at DL2, 2 at DL4, 4 at DL5, 24 at DL-1 and 13 at DL-2)

• 20.8% of pts remain alive at 36-month post PVSRIPO infusion, compared to 4% of an historical control.

• Four pts remain alive more than 22 months post treatment without having received any additional intervention following PVSRIPO at 57.5+, 56.4+, 27.9+ and 23.2+ months.

An important thing to keep in mind is that the patients in this phase 1 trial were treated with various doses of the virus.  We can expect future trials that move forward with the approximately optimal dose to have better overall results than this trial.  The first patient in this trial is now 5 years in remission.

http://abstracts.asco.org/199/AbstView_199_192524.html

Upcoming trial of modified poliovirus for children ages 12-18 with recurrent malignant glioma

The anticipated start date is June of this year.

Phase Ib Study of Oncolytic Polio/Rhinovirus Recombinant Against Recurrent Malignant Glioma in Children
NCT03043391

RVSRIPO AND CHEMO

Well, I guess PVSRIPO is relevant to cocktail approach.  What I thought was the most promising in the CBS report is that when they added chemo later to one the treatment had failed on, it actually had a complete response. The immunotherapy made tumor more vulnerable to chemo. I'm surprised they were all surprised by this. This just confirms the future must be a cocktail approach and not a silver bullet.

Grace and Peace,

Danny  

Polio/Rhino Virus

I know this isn't cocktail related, but CBS is doing a follow-up this Sunday. There is no question, a single therapy that eradicated recurrent GBM is stunning. I'm just wondering how we should view this? I don't believe there is such a thing as false hope. But, is this more media hype or a breakthrough? http://www.cbsnews.com/news/promising-duke-university-polio-brain-cancer-trial-given-breakthrough-status-60-minutes/

Chance's latest (this month) MRI showed edema

At Chance's MRI on 9/11, edema was found. Chance had been getting increasingly dizzy. Within the last couple of weeks he left his job on short term disability because he had several times he referred to as his brain not working. He could not put words together to explain he was having a problem comprehending or communicating. His position was in high stress software sales, so it was probably the last thing he should have been doing, but of course he wanted to keep working as long as he could.

His NO suggested he increase the Decadron to 4mg a day (he was finally down to 1 mg a day).

A worrisome MRI happened once before, last spring, so we prayed we could wait 30 days and have him retested, but his case went to the UCSF tumor board on 9/17 and it was agreed edema was caused by progression and that his tumor was now inoperable because of it's location - near language and memory.

The board suggested Avastin and CCNU.

Based on what I've learned these last few months, I had no problem saying NO!

Stephen gave me some trials to consider, two at UCSF and two at Duke. All but one required some sort of surgery, so we went with the least invasive: Toca 511 at UCSF. Chance will be the first participant in Cohort 7, which means they will use an infusion in hand or arm, rather than placing the virus directly into the tumor. They say it has been proven that the virus gets to the brain regardless of where it is given. He will have the virus infusion over three days starting next Monday. A month later they start a dosing with an anti-fungal that becomes a powerful chemotherapy agent to kill dividing cells. He will take the anti-fungal pills every six weeks for four cycles. The beauty of this particular trial is that it has a continuation arm.

For those unfamiliar with Toca 511, there is a lot on YouTube you can find by searching "Toca 511". It is being offered at nine locations in the U.S.

We are consulting Duke for a second opinion and treatment options just to get a foot in the door in case we want to pursue in the future.

I wanted to update Chance's status and include a huge shout-out for Stephen, Ben, Rich and Cheryl and so many others for everything they have done and are doing for their GBM sisters and brothers. I am grateful beyond measure.