Replies to post #79514 on NorthWest Biotherapeutics Inc (NWBO)

[flipper44]

RK, the only way I would go over 6.6 months PFS post randomization (9.7 months post diagnosis) extreme high case scenario for placebo in the phase III trial is if I had a different understanding (than I do now) of the definition of intent for gross total resection.

My understanding is that they are considering tumors that are supratentorial. Beyond that, they will not accept biopsy surgeries into the trial. That means there will be a substantial amount of partial resections, even though there was intent for gross total resection.

In the main group for the Rindopepimut trials, there was 100% resection in all trial patients, and at the highest in all their trials, as I think you pointed out, there was a median PFS of 12 months post randomization (in another trial they were down to 9 months). I don't think the DCVax-L trial is getting anywhere near 100% of 100% resections based upon their inclusion criteria, and other than lacking biopsy patients, will likely come much closer to the typical patient profile.

Thoughts? (P.S. Obviously, for purposes of this inquiry, I am setting aside other factors previously discussed by both of us that may or may not affect PFS)

[sentiment_stocks]

So I'm assuming that the absolute lymphocyte count required in the US of ≥1,000/mm3, and the fact that this is 1/2 that amount in Germany - absolute lymphocyte count ≥0.5x10E3/mm3 or .5 x 10^3 = 500/mm3 - is NOT a mistake, correct?

There are so many balls in the air here that I can hardly keep up, so forgive me if this has all been established.

Your thought is that the German patients were the ones who "would take account of such a major variable" because their entry into the trial began after August 2014, correct?

Most importantly, the recent research has identified a major impact on these GBM patients’ Overall Survival (OS): the variable relating to severe depression of white blood cell counts can make a difference of 6 months in OS. As a comparison, the standard of care drug for GBM, Temodar, only makes a difference of 10 weeks in OS. If the statistical analysis of GBM trial results does not take account of such a major variable, the overall trial results could be significantly skewed.

Under the enhancements to NW Bio’s Phase III trial, the statistical analyses of the trial results will be modified to take account of, and control for, this important new variable. - August 2014 PR

http://www.nwbio.com/nw-bio-obtains-approvals-for-enhancements-of-phase-iii-trial-of-dcvax-l-for-gbm-brain-cancer/

So does anyone think then that those German patients presenting with the lower lymphocyte count were then to be relegated to their own arm... much like the psPD's were given their own arm? Otherwise, wouldn't these lower lymphocyte count patients conflict with those patients in the trial who had to present with a higher lymphocyte count?

If that were the case, would it be possible that the main arm was almost fully enrolled, if not fully enrolled, and then when the screening halt was implemented - maybe July or August 2015, it may have involved some of these German patients (?) where the screening halt perhaps started?

Just thinking out loud here.