NorthWest Biotherapeutics Inc (NWBO)

[jammyjames]

Back again...been away and offline for the weekend….i see the arguing has continued! haha

Right to get back to this point flip. Ofcourse it’s a single arm retrospective study...i’m just trying to get a better idea of how placebo might behave in the current P3 DCVax-L trial. Regarding your point “Brandes case is not helpful for determining efficacy for standard of care, because 50% of the population was excluded for arbitrary reasons”

I would suggest that 50% of the population were not excluded for arbitrary reasons, in fact the reason is quite obvious as to why and which patients were excluded from Brandes et al., 2008. If you’ve ever done bisulphite sequencing/genotyping you’ll know that you lose most of your DNA due to conditions needed for complete conversion of C>U. Hence when you’ve only got a biopsy from a tumour with only a few nanograms of DNA this can easily lead to failure of the genotyping step. So it’s no surprise in Brandes et al., 2008 that they only have a couple of biopsy only patients in their cohort since the biopsy only patients were the most likely to fail genotyping. Therefore I would suggest that this population (yellow line fig3 brandes et al., 2008) is actually quite representative of the placebo group in the current DCVax-L P3 trial as there is a clear link between exclusion due to not getting enough DNA from the tumour tissue and exclusion due to being a biopsy only patient.

Regarding your point “it's been explained repeatedly on this website that most trials exclude rapid progressors. Optune, ICT-107 and Celldex all excluded them”

ICT-107...i can’t see anything in the exclusion criteria about excluding rapid progressors https://clinicaltrials.gov/ct2/show/NCT02546102
Celldex...looks like they excluded both rapids and pseudos “No evidence of progressive disease from the post-operative period to the post-chemoradiation period” https://clinicaltrials.gov/ct2/show/NCT01480479
Optune…the clincialtrial info is a bit unclear.... “Progressive disease (according to MacDonald Criteria). If pseudoprogression is suspected, additional imaging studies must be performed to rule out true progression.” https://clinicaltrials.gov/ct2/show/NCT00916409 but the 2015 JAMA paper seems to suggest that both rapids and pseudos were excluded.

so I think you’re point that “had the rapids in the Brandes trial been removed and only the pspD and nonpsPD been included, the median would have been 28” is kind of irrelevant.

By the way I agree with you that if the placebo arm comes out at 21 months this won’t necessarily screw DCVax-L. I forgot to adapt my analysis for the enrollment for those 10% of patients who’ve been in since 2009 and earlier. Anyway here’s my current view of how the end points will come out for non-crossovers (assuming no placebo effect).

Blended mOS: 24-25 months
placebo mOS:19-20 months
DCVax-L mOS:26-27 months

Yes I know PFS is the primary end point but i’m sticking to analyzing OS for 2 reasons:
1) At the end of the day it’s the more important readout
2) It involves less hand waving (though I know this is a popular activity on this ihub board)….we have concrete numbers for the enrollment timeline and number of patients alive and lost on the 5th June 2017.

So overall I think the results will be good but not quite the improvement that i’ve seen touted by others…..i’d be happy to be proven wrong!