NorthWest Biotherapeutics Inc (NWBO)

[AVII77]

Do you really think that first, the DMC would have the power to do that in the DCVax-L trial, or simply the ability to recommend it to the company?

I believe the DMC only has the power to make a recommendation.

However, I believe the company has an obligation to relay that recommendation to the FDA. Though that is debatable. Consider the disclosed correspondence surrounding the Cel-Sci futility rec
From Page 6 of their 10-k

In its partial clinical hold letter, FDA identified the following specific deficiencies: a) FDA stated that there is an unreasonable and significant risk of illness or injury to human subjects and cited among other things the absence of prompt reports by us to the FDA of IDMC recommendations to close the study entirely (made in spring of 2014) or at least to close it to accrual of new patients (made in spring of 2016); b) FDA stated that the investigator brochure is misleading, erroneous, and materially incomplete; and c) FDA stated that the plan or protocol is deficient in design to meet its stated objectives. In its partial clinical hold letter, FDA also identified the information needed to resolve these deficiencies. In addition, FDA’s partial clinical hold letter included two requests relating to quality information regarding our investigational final drug product, which were noted by FDA as non-hold issues. CEL-SCI believes that its response submitted to FDA on November 18, 2016, addressed each of the deficiencies identified by FDA including detailing our belief that, under the applicable FDA guidance, there was no obligation to report the cited IDMC recommendations to the FDA at the time they were issued, and it also requested a face-to-face meeting with FDA, and outlined our commitment to diligently work with FDA in an effort to have the partial clinical hold for the study lifted. On December 8, 2016, the FDA advised CEL-SCI that the agency was denying CEL-SCI's request for a meeting at this time because FDA's review of CEL-SCI's November 17, 2016 response was ongoing. CEL-SCI was also advised that it will be receiving a letter addressing CEL-SCI's response by December 18, 2016.

So Cel-Sci and the FDA have a disagreement on the answer to your question.

And second, wouldn't you think if they had recommended it, the company would in turn... knowing that the patients were living longer... not accept such a recommendation?

Yes, I agree. (Though I question the "patients were living longer" aspect. The patients were not "living longer" than theorized in the new protocol).

If the DMC indeed had such a power, don't you think they would have considered that a good many of the patients were actually living longer?

Even if they did consider that, the Primary Endpoint is PFS, if that is futile ethics would preclude asking more patients to participate in the study (designed to see if there is a benefit in PFS).

We don't know for certain that MRIs were showing progression, but if they were, we can theorize that they were in turn disappearing after a period of time, especially if the patients were living longer.

Agree, we don't know MRI's were showing progression (futility); we are connecting dots.

Sure we can "theorize they were in turn disappearing" but (and here perhaps is our primary disagreement) there is nothing you can do to salvage the trial.

You can maintain the blind and follow for OS (and probably should). But (and this is our other disagreement) what would the data mean (if the primary indeed fails)? And, What is the likelihood the OS (now exploratory) would show an advantage of DCVax.

For me, seems that "all the dots" point to a finding of futility.

I'm have a problem seeing how the DMC could have enacted this temporary screening halt - when they likely only had the authority to recommend such a halt. IMO, that just doesn't seem to be the right decision or the correct approach to take, given that there was OS waiting in the wings. Anyone remotely familiar with immunotherapy trials should have known this, don't you think?

Dr. Furberg, the Chairman of the DSMB, is a renowned clinical trialist. If there was alpha left to test OS, then it would be fine to continue randomizing patients. If not (and there is not) then you stop randomizing patients. It's as easy as that Senti. "Anyone remotely familiar with" clinical trials knows this.

(and a respected poster here noted Furberg is no longer on the DSMB - another dot).

And the DMC must have been aware that pseudo progression could be caused by DCVax itself as Linda Liau also said this herself in her March 2012 video.

Maybe so. But then since PFS is the sole primary endpoint "the plan or protocol is deficient in design to meet its stated objectives" and the FDA initiates a partial clinical hold to prevent enrollment of additional patients.

When the sponsor throws in the towel and agrees not to enroll additional patients the hold (on the still futile trial) is lifted.