Why is the SAP being re-written and why is there continuing vagueness of the timeline for data lock("progressing" toward whatever that means)/unblinding? I believe this is essentially the question you are posing and I am attempting, poorly it seems, to respond.
Allow me to dumb it down:
1. The trial is blind;
2. Until unblinded, no one knows for sure whether the primary/secondary, indeed any, endpoint results have been sufficiently achieved in order to warrant reg approval;
3. LP, at the ASM has explicitly declared that they have the "petal to the metal" and have many experts and cannot throw more money to make the whole process go faster;
4. Further, with all these experts, LP has much more info than outside shareholders have and thus have a pretty good idea as to the likelihood of meeting the primary/secondary endpoints;
5. Due to pseudo progression, cross-over and other factors, all these experts have serious concerns that these endpoint results may likely( although they are not sure)fall short and not be SS;
6. Accordingly, LP and her advisors are focusing upon the OS milestones, length and thickness of the long tail as well as its composition(for example, how much M+, M-, cross over arm, non-cross over arm,etc.);
7. Therefore, dragging of feet to finally go to data lock and providing clearer timeline guide lines. They probably feel that a grand slam homerun on the milestones/tail will overcome any failures on the primary/secondary endpoints;
8. Thus, the delay in ending the trial as they want to have enough data to make the results "undeniable" as LG stated on 4/27/18;
9. They want to re-write the SAP in order to shift focus on the OS milestones/ long tail and diminish importance on the primary/secondary endpoints which may not be appropriate for immunological approaches. After all, the original SAP was written before the importance of long tail in immunological approaches was entirely appreciated;
10. They probably had many give and take discussions with the FDA ( and other RAs) and while they have the FDA's understanding and a more flexible attitude, the FDA has probably told NWBO that while long tail is important they will look at the totality of the data within which to consider reg approval.
Thus, bottom line, I think that the foregoing implies that the trial probably did not achieve unambiguous results for primary/secondary endpoints and that NWBO pretty much knows that--but not for sure. Thus, the overwhelming focus and reliance on milestones/long tail. Thus, the continuance of the trial to have enough mature data to make their approval case undeniable and the re-writing of the SAP to shift focus from the primary/secondary endpoints to OS milestones/long tail.
My feeling is that even though the primary/secondary endpoints may not be unambiguous or have fallen short, the long tail results will be homerun enough to warrant approval, especially if results are comparable to those of Optune and have the added benefits of QOL and long tail info and results.
I hope this exposition clears up the confusion engendered in my previous post on this matter.
