Replies to post #104453 on NorthWest Biotherapeutics Inc (NWBO)

[GoodGuyBill]

Thanks Sentiment-stocks.

Based on your comments below, NWBO may have an issue meeting its PFS endpoint #s because patients with pseudo-progression (caused by DCVax-l) are deemed to have disease progression (since there is no process within the trial protocol that seeks to distinguish between the two).

If LL was growing aware of it in 2012 when she told her tale of two tumors, then she may have been seeing it by 2011/2012 in the trial. But by then, there was a prior protocol that most likely delineated exactly how progression would be read, and as I went into some detail in post #102956, that there are no words in the April 2013 protocol about "waiting and seeing" and then doing another MRI in a couple of months. There is no baseline MRI AFTER you enter the trial that is written about in the protocol. RK believes that it is being done because MacDonald criteria does this. But that is NOT what is in the protocol. And so, IMO, it really doesn't matter what any other assessment criteria does or doesn't do. It's the protocol that calls the shots here.

[marzan]

Senti, if that 20% wrongly counted PFS patients indeed are part of the Longtail survivors, then that 20% patient numbers should be deducted from the overall PFS events at the end and mPFS should be recalculated. After reading your post, I want to reread exact wording of what LL said after the lift of the screening hold by the FDA. It might contain lot of meaning. Did she say Good FDA lifted it??

[mapman1010]

damn senti, i mean WOW damn senti.. :>). Bravo. if i could compose my thoughts as well as you do yours i would say nearly the same things. TY

[Doc logic]

sentiment_stocks,

Now this is the conservative approach to take in regards to the analysis of where we are in with regards to the trial. As an aside, I would say that evidence from UCLA with regard to biomarker analysis and imaging to determine mesenchymal subtype have put FDA in a place where their actions must alligns with evidence and what is best for pstients. The gray areas of analysis are rapidly being made clear. Best wishes.

[antihama]

Hi Senti, the last couple of days took me away from this board and I just got back on and I know I got a lot of catching up to do but before I catch up, I wanted to respond to your post w/o being influenced by the, I’m sure, lot more discussion on this topic. Here’s my reason why I think that psPDs may not have been removed from the trial. Regarding

And if they put that passage in to determine psPD before randomization, why didn't they put it in for those patients who might falsely progress after randomization? Well I think it's because they didn't realize that psPD could happen from DCVax... just TMZ and RT

It could very well be what you say is so but I believe if they did know in 2013 that psPDs could happen w immunotherapy then I would think they would follow standard practice at the time. Say you are a radiologist in 2013 and everybody knows that you need multiple scans to determine psPDs why on earth would you declare a pt has progressed on 1 scan? Because the protocol didn’t go into detail on what to do? I don’t think so. I have to tell you in a previous life I used to audit pre-clinical protocols (the caveat here is that clinical protocols may be different but not by much). The pre-clinical protocol spells out in general detail what you are supposed to do e.g. draw blood at x,y, and z timepoints and analyze for drug abc. The protocol doesn’t tell you any more detail than that but somewhere you know what you need to do. You are going to have a method on how to analyze those bioanalytical samples and the method is going to tell you exactly what you need to do to. There is going to be a Std Operating Procedure on how you validate a bioanalytical method, on computer system validation, on pipette, and weighing scale calibration etc so there is a lot of stuff that you don’t see in the protocol. I’m sure a radiologist will have SOPs that guide them on what to do when encountering a psPD patient. I see from the consent form that was recently referenced that MRIs are given every 2 months (month 2, 4, 6, 8 etc). Why wouldn’t you wait for the next scan or 2 to make that determination? I just don’t see it. Regarding

Information Arm, that enrolled in 2008, 2011 and 2012, had 25 patients that the very professional radiologists (the same ones used in the trial) couldn't determine what they were.

Hard to argue against your point. Just wondering if for the most part those pts were recruited early on when radiologists still weren’t sure about what was happening. So, the Q that comes to mind is when did it become common wisdom that psPDs could be a good thing? Regarding

And if 3 out of 15 patients in the P1 trial (20%) - the best performing patients I believe - all showed false progression that would have deemed their response a progression event in this trial, well then, I'd suggest to Houston that we have a problem.

Ditto on wondering if for the most part those pts were recruited early on when radiologists still weren’t sure about what was going on.

As we patiently wait.