NorthWest Biotherapeutics Inc (NWBO)

[flipper44]

You do realize you are making any potential excellent results in the main group that much stronger because you are arguing they squeezed out every known and likely early pseudoprogressor from the main trial. It looks to me like they admitted when they did miss a diagnosis and accidentally placed one pure pseudo into the info group. The main trial arms (treatment and placebo) are made up of homogenous patients. No other trial to my knowledge has tried to exclude the majority of pseudoprogressors from the main arms of the trial.

Why would NWBO do this and other trials not do it? I suppose your response would be because NWBO did not know any better. No! Instead they knew they were reducing the likelihood their trial would have the longer lived pseudoprogressors in their main comparison arms.

While other trials attempted to rely upon the well known longevity related to pseudoprogressors receiving SOC to perhaps pad their overall trial numbers, NWBO created a homogenous trial group. That is considered a gold standard.

It is not without risk, because without the pseudoprogressors, the likelihood is that overall pfs and os stats for the trial would be shorter. For instance, in a very large trial using the Stupp protocol versus the Stupp protocol dose dense, it showed both treatment groups got around the average median numbers. About 6 to 7 PFS and about 15 to 16 for OS. Had they excluded the early pseudoprogressors, those numbers could have possibly dropped to about 4 PFS and 12.5 OS. (By the way, there was no statistically significant difference between dose dense temodar versus regular dose Temodar.) For any trial, overall 4 pfs and 12.5 OS would look terrible, even if one comparison arm slightly outperformed another.

For all practical purposes, if this DCVax-L trial were instead only SOC patients, and pseudoprogressors were not removed, I'd argue the trial would already be over a while ago. IMO. If it was all standard of care and they instead excluded all early pseudoprogressors, it would be over a much longer time ago. IMO.

Here is what the researches have been telling us in a nutshell -- I'm my own words.

1. DCVax-L has very limited effect in rapidly progressing tumors.
2. DCVax-L has somewhat limited effect in mostly nonresected tumors.
3. DCVax-L has very powerful effects in pseudo-progressive "tumors".
4. DCVax-L has effect in stable post-resected tumors.

The main arms of the trial are for number 4 above. The pseudo progressive arms carrying a total of 32 patients are obviously for number 3 above.

(By the way, the German label did not show that 35 pseudos were enrolled into the information arm. IMO)

In my personal opinion, without any improvement, this trial should have reached 248 PFS events a while ago. The latest PR commenting on enrollment states we are "well over" 300 enrollment (I assume they got to that number by October 30, 2015). Without early pseudoprogressors in that group of "well over" 300, the further we go out from here, the more likely the world will see a new option for GBM care. IMO.