Koman,
If PFS difference between the cohorts falls short of significantly it does not mean that the study is destined to fail, and that the vaccine is nothing but a placebo. Even AVII has acknowledged that reputable scientists are able to show patients are responding. Whether that response is meaningful enough, time will tell. But you're ascribing failure of an endpoint to mean the end of the study and that may not necessarily be the case. Perhaps an IA has found the vaccine not to be impressive at keeping recurrence at bay (primary endpoint) that doesn't mean it won't be found to be successful at postponing death (secondary endpoint).
You of all people know I've been concerned about PFS may fall short of significance for a while. It was the original reason I sold my shares last summer. I understand how well a placebo arm can do. Alarm bells rang for me over the company taking all the credit that was due to multiple variables, which contributed to some of the impressive PFS and OS earlier study results. It took a few trials results to air for folks to finally see my point on how well a placebo arm can do with the inclusion criteria this Ph III trial is privy to. But even I understood that a part of the impressive results may have been due to the vaccine, I wasn't all dark. At a certain point even the best standard of care the cancer comes back for most patients. The GBM recurrence rate is alarmingly high. In the case of DCVax-L earlier studies, for a number of patients the disease didn't return. Skeptics in my opinion have gone too far and not given the vaccine any credit and a decent percentage of overall survival may be due to the vaccine. Time will tell if it deserves such doubt.
Let's say that an IA was done in August, as you suggest it was, if the study proved completely futile then the decision to end it would be easy one. However we sit at a "no decision had been made" point in time. The only thing we know is that there is a risk that regulators may not lift the screening halt. If AVII is correct and the independent radiologist review are determining PFS events, and those turn out not to be "true" PFS events (due to immunotherapy inducing psPD condition) then those patients will crossover and in theory go on to live a long time. That early PFS event would have a negative affect on the TX arm's ability to show a time to progression difference if it occurs often enough in the TX cohort. But on the flip side, overall survival would be extended for those early event patients, hopefully you see that.
If your IA theory is correct and PFS is weak (I don't doubt this possibility), NW Bio could be behind the scenes easily arguing that outdated iRANO standards affected the PFS data, and they would have the data, eventually in time to prove it. The regulators may have a hard time justifying adding more patients to a study that has been running since 2008 before they see convincing evidence that it is helping on OS. Even they could be skeptical of Management's COI. That would be understandable, this company has changed their trial more than most. But, that said, I would expect the regulators to analyze the OS events of a number of those PFS patients before they decide whether or not to allow a protocol amendment to pass (to adopt a change to accommodate new iRANO). They wouldn't just veto it and say no. This is an orphan disease that needs more treatment options. Plus, we already know patients are living longer in this trial, if we go by Linda Liau's words. We just don't know if it's due to the vaccine or not. Neither do they. What do you do in that kind of situation? You'd watch events, which is exactly what they might be doing now. If you're theory is correct, the fact that regulators have not stopped the trial for over for over 8 months now, while the patients continue to be treated, to me means the results reveal something of interest at crossover and they are watching it. The PFS would not be a real event if it happened at month 4, but yet the patient is still alive at month 25, regulators will understand that, particular if the neuro-oncology community is suggesting the imaging criteria needs to change. And if the regulators decide in a few months that the study is to far along now to change it, then the company will just issue a press release that the trial recruiting is closed (they probably won't mention the halt) and they'll tell us the number of enrolled patients they're at; all patients will continue with their treatment according to schedule and the study naturally ends at some point. I suspect they will never tell us what the submission was about, but in the end the results will speak for themselves. If iRANO hurt the primary endpoint then the secondary endpoint will be strong. And if it isn't, the vaccine will not be approved in any subgroup. We'll all find out when it happens, according to SEC rules.
