Replies to post #512758 on NorthWest Biotherapeutics Inc (NWBO)

[SkyLimit2022]

The FDA and NIH work very closely together. Highly reputable licensed professionals have vetted the immunotherapy research of Dr. Liau, I would recommend that you research and study for yourself the recent 590 million dollar grant that was awarded to UCLA. The U.S. government NIH grant is funded by tax dollars and is public record for anyone who wants to see it. Many independent physicians have reviewed the immunotherapy work of Dr. Liau. Verify it for yourself.

The NIH peer-reviewed grant is the source of funding being used today to dose patients with DCVax-L and Keytruda.

Department of Neurosurgery Chair Linda M. Liau, MD, PhD, MBA, was a leading recipient of NIH grants – No. 3 in the nation within the discipline.

“It's the stamp of approval from the NIH, because these types of grants are so rigorously peer-reviewed,” Dr. Liau says. “People get funded based on the strength of the science and that, itself, is very powerful in terms of showing that our research is scientifically valid and meaningful and hopefully will lead to future treatments.”

https://www.fda.gov/science-research/advancing-regulatory-science/fda-nih-joint-leadership-council-charter

https://connect.uclahealth.org/2021/03/22/ucla-received-590-million-in-nih-funding-second-highest-total-for-academic-medical-centers-in-2020/

Dr. Pazdur, FDA:
https://www.annalsofoncology.org/article/S0923-7534(22)00006-0/fulltext

[SkyLimit2022]

That is correct—OS is the gold standard.

Anyone can research to verify that PFS is a surrogate for OS and only used because its data is accessible sooner than OS. When and if OS is reached, OS data either confirms or disproves the accuracy of PFS as a surrogate and as a PREDICTOR of survival. OS naturally became a “hard endpoint” for the P3 as the trial spanned so many years.

“OS is the "gold standard" for measuring the clinical benefits of a cancer drug. The global trial has also reached the secondary endpoint of OS in recurrent GBM with statistical significance.”

“The ultimate goal of all oncology drugs is to improve patient-centered endpoints. These 'hard' endpoints, which are intrinsically valuable to patients, are increased overall survival (OS), improved quality of life (QoL), or both. However, by many drugs are approved or used based solely on their ability to improve surrogate endpoints; outcomes that are not inherently meaningful, but aim to predict hard outcomes.”

“In oncology, the most commonly used surrogates are response rate; a set of criteria characterizing tumor shrinkage; and time to event endpoints, such as progression-free survival (PFS)”

Overall survival is the gold standard and remains the definitive end point in cancer clinical trials.

Quite simply:

You cannot mistake
the dead for the living.
That is why OS is the
gold standard.

[meirluc]

HyGro, the so called post hoc, data dredged recurrent GBM arm, composed of 64 crossover patients, is the major success story of this trial. Even when combined with the 35 non-treated placebos, the mOS of this group of 99 patient "intend to crossover group" is about 24 months. The OS curve of those 64 crossover patients has not as yet been revealed by the recent major presentations (NYAS, UK, Prague) because IMHO, this is being held as a major surprise to be revealed in the publication.

Hint: given that far fewer patients' recurrent tumors than patients' initial tumors can be resected and utilized as vaccines, why has the UCLA combo trial (which employs DCVax-L in both arms of the trial), conducted the trial in rGBM patients and not ndGBM patients?

Answer: 1. the recurrent vaccines are more effective in rGBM than ndGBM patients most likely because the recurrent tumor's increased mesenchymal phenotype signature increases its vulnerability to the vaccine.
2. Furthermore, the recurrent vaccine is more homologous to the recurrent tumor than a vaccine prepared from the ndGBM tumor and would therefore constitute the more effective vaccine.

In my opinion answer #1 is the reason that at least up to 24 months on trial, the group of 99 crossovers had a much better survival record than the treatment group and that surprising result is solely due to the astounding survival capacity of the 64 crossovers. It is especially astounding since the 35 never L treated patients had a very short mOS.

[Roman516]

Thats great as PFS is a statistical objective but once again per normal some posters just continue to be confused and confounded. The good news is that the OS data prevailed, and the doctors, scientist and professionals agree that the OS was in fact impressive to say the least. Time to move on per
the FDA guidance, Clinical trial endpoints, approval of Cancer drugs and Biologics

With respect to NWBO and DCVAx=L
ALL of these endpoints are accepted for FDA approval consideration.
- Overall Survival, OS results surpass PFS predictions
- Disease-Free Survival (and Event-Free Survival), Survival better than current SOC
- Objective Response Rate, at least 2.5X that of present SOC chemo poison
- Complete Response, Same as above and potential longer timeframes, great OS.
- Time to Progression and Progression-Free Survival, again at least 2.5X that of present SOC chemo poison.
- Time to Treatment Failure, at least 2.5X beyond that of present SOC

Based on the real facts about DCVax-L, this is looking better than the current SOC chemo poison, IMPO.
Looking forward to more good news as NWBO moves forward

[biosectinvestor]

There was no post hoc data dredge and they knew that they had this crossover arm and could look for the same benefit as they had with the treated patients using the external control arm. All of it was approved before unblinding. You use the data dredge term that AF uses with other trials all the time because it sounds serious. It didn’t happen here. Sorry. What was measured was what they decided to measure given the circumstances and the previous determination to let the trial run and get the survival data. If PFS was the aim, the purpose of that endpoint is explained in my other posts and they’d have ended things earlier. The purpose of PFS is to get an early result.

OS is a concrete result, not a correlation with survival, but survival itself. Data dredging is for surrogate results, not a concrete result like beating hearts at the end of a trial where beating hearts typically no longer remain.