NorthWest Biotherapeutics Inc (NWBO)

[AVII77]

Without any DCVax-L treatment effect the maximum expected combined cohort OS would be 24-25 months as a combined grouping for a patient population matched to Dr. Linda Liau's reference group and the the group of high mid range positive patient characteristics found in a chart posted by AVII77 recently.

Good to see you using "combined cohort" because that's how you should approach this.

Assume DCVax and Control are equal and figure out what you expect the KM curve to be for the patients enrolled. (Considering things like no biopsy's, no progression after primary treatment verified by MRI, no or little steroid requirement, - and on the flip(per) side the potential for selecting against longer-lived MGMT+ patients).

That would be the "control" arm survival (and the treatment arm survival if the treatment has no effect).

Your 24-25 months is a bit high IMO. I think Control will do slightly better than the ACT IV trial (ITT). Maybe 20-22 months.

If there is a 3 month benefit in OS with a non toxic treatment in GBM which has an orphan disease designation, approval is basically guaranteed.

We'll use your numbers.
If control does 25 months and DCVax does 28 months then, with 233 events the p value would be about 0.42.

Not even close to stat sig. Not by a mile.

To hit SS you would need 1350 events. And that would just get you 0.05 (the FDA wants better than that for single trial approvals).

So yeah, the FDA might approve it with a 3 month advantage, but they are not going to show a 3 month advantage with only 233 events.

BTW, when I modeled the OS here this is what I got (blended).

And I have reason to believe the control arm (as you note above) will perform even better than the ACT IV trial (who were all EGFR+).

There was no incentive to do any unblinded analysis if the best outcome NWBO could have had by doing one was a recommendation to continue the trial,...

Do you think it might be good to know if the trial, as planned, has any reasonable chance of success? You know, to avoid lying to patients when you enroll them saying "please help us find out if DCVax prolongs the time to progression". Ever hear of the Belmont Report or the Declaration of Helsinki?