NorthWest Biotherapeutics Inc (NWBO)

[AVII77]

You would agree however that because they remove suspicious psPD and rPD at the 1st baseline, the trial converts to RANO's 12 week delay standard by default, because the second baseline is at 12 weeks post chemoradiation. (Giving many psPD a chance to calm down).

No Flipper, I emphatically disagree.

Forget Baseline 2. There is NO Baseline 2 for those patients included in the primary efficacy analysis.

(Baseline 2 ONLY applies to the randomized psPD cohort. They are separate and distinct from the main randomized cohort)

Two weeks after completion of primary chemorad a patient has his Baseline scan.

This scan determines if he is, or is not, allowed to be randomized into the trial.

Once randomized, assessments begin every 2 months.

At that first assessment at 2 months (10 weeks post chemorad), if he exhibits progressive disease on his MRI he is counted as a progression event.

Period. Full Stop.

I'll paste again at the bottom of this post my annotated treatment schedule (from the patient consent form available on the UCLA site)
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So, the only patients that would be excluded are the rPD and psPD that are expressing that progression 2 weeks after chemorad, not 12 weeks after chemorad (as in RANO).

If you can show me literature that demonstrates an assessment made 2 weeks after chemorad filters out the bulk of rPD and psPD patients, you will change my mind. (And we can together inform the RANO committee and share this important info because for some odd reason they felt 12 weeks would be more appropriate).

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Furthermore, you should understand the the MOTIVATION for developing this RANO 12 week criteria was to reduce (not eliminate) the enrollment of psPD (not rPD's) in clinical trials studying recurrent GBM.

It is not meant to diagnose psPD (HWM4life's diff di), it is meant to enhance the interpretive significance of rGBM trials because people were enrolling these psPD's into rGBM trials and mucking up the results.

And this is PRECISELY what happened in the info arm data. The BS Info Arm data that the company is pumping is a rGBM data set. And psPD's are STILL IN THERE because those patients were put in there at 2 weeks after completion of chemo rad. This is true for ALL their groups but ESPECIALLY true for the "indeterminant" group they are pumping.


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Furthermore, this whole topic has been twisted by NWBO. As proof they are twisting the truth, consider carefully what LP says here.

She says (regarding the info arm patients) that they are "basically always excluded from GBM trials because their variation is so aggressive you just can't help them.".

That's not correct. That is total PUMP!!!

They are excluded from GBM trials because they may be psPD patients. psPD patients NATURALLY have the response shown on their MRI's resolve with time. If they were included in studies looking at rGBM patients their natural resolution could be wrongly attributed as a response to the treatment from whatever drug is being tested.

"A proportion of patients enrolled in clinical trials for recurrent GBM will have had pseudoprogression at the time of enrollment. Pseudoprogression may alter the interpretation or perception of subsequent drug response, given that pseudoprogression on MRI may improve spontaneously without therapeutic intervention and that such patients typically have a favorable survival. One obvious way to manage the proportion of patients with pseudoprogression is to limit the minimum time from the end of radiation therapy, when patients can be enrolled in trials for recurrent GBM. If we limit patients with disease progression to those who are at least 6 weeks from the end of radiation therapy, we can expect no more than 20% of all patients to have pseudoprogression, with longer intervals from the end of radiation therapy leading to smaller rates of pseudoprogression."

These 51 patients were assessed 2 weeks post radiation therapy. We would expect ~20% to be psPD patients. How many are still living? 10 of the 51 patients remain alive. (Anyone here good at math and can figure out what percentage that is?)

This is precisely what may be happening here with the "info arm". They are rGBM patients, no argument there. Some rGBM patients are psPD others are real PD patients. Other trials looking at rGBM patients would exclude those with early signs of progression not because patients are "too sick to be helped" but rather because some of them are psPD and any response in those who are psPD may be wrongly attributed to the drug. "Manipulation and misinformation"? She wants you to believe they have "incredibly aggressive" disease and she misinforms you of the REAL reason they are excluded from trials examining rGBM, suggesting instead miraculous results (wrongly attributed) to DCVax. (it MAY be DCVax, but there is NO way to tell. The one thing we can be sure of though is that we would expect psPD's to be in there)

It blows me away that you guys can't see through this hype.
You are indeed being manipulated. You think it's by me, LOL. Guess again.

Anyway, I guess I went off on a bit of a tangent there Flipper. But the concepts are totally related. I'll respond to your second sentence in a separate post. I'll try to be more succinct (no guarantees).

TLDR: No. I don't agree.


Below is the assessment schedule (w/my annotations) from the UCLA consent form.

The "A" and "B" relates to a previous discussion.

The question there was: If a patient passes MRI “A” (not progressing and therefor randomized) and then, 9 weeks later after receiving 4 doses of DCVax or placebo, fails MRI “B” what happens? (this is the scenario with the 3 patients Dr. Liau identified).

I assert that he will be marked as a progressor at the time of MRI “B“.