Replies to post #520137 on NorthWest Biotherapeutics Inc (NWBO)

[SkyLimit2022]

Thank you for again highlighting the exemplary trial design—compassionate, clinically appropriate, adaptive, and representative of DCVax as an innovative new platform technology.

The trial design and its endpoints were approved by regulators multiple times. Each country or union of nations has its own RA—Canada, Germany, U.S. and the union of nations U.K. all have RAs. Each approval was a separate and distinct RA approval.

Beyond approval by multiple RAs, the trial design was approved multiple times by the FDA—the crossover design, for example, was approved twice by FDA because there was a trial halt, and then the trial was approved to resume with the same crossover design it previously had.

The MHRA in U.K. approved the trial design and its endpoints twice—once for the adult trial and now again for the pediatric trials:

On August 17, the Company received final approval of the Pediatric Investigation Plan (PIP) from the MHRA. The final regulatory approval of the PIP must be obtained before a sponsor may submit a Marketing Authorization Application (MAA) for approval to commercialize the new medicine for adult patients. The Company’s approved PIP includes a deferral under which the pediatric trials are anticipated to be undertaken after an MAA application has been submitted.

Patients will be treated with DCVax-L on the same treatment schedule as in the Company’s Phase III trial in adult glioblastoma patients.

The primary endpoint for each of the 2 pediatric trials will be overall survival, determined by comparing the survival of DCVax-L treated patients to matched contemporaneous external controls. The external controls will be identified using the same methodology as was used to pre-specify the external controls in the Statistical Analysis Plan for the Company’s Phase III trial in adult patients.

https://virtualtrials.org/dcvax.cfm

https://www.kcl.ac.uk/people/keyoumars-ashkan

https://nwbio.com/press-releases/

More recent news and events:

Dr. Ashkan, a world-renowned clinical trial expert and an advisor to the U.K. government, presents DCVax P3 data.

https://soc-neuro-onc.org/
Autologous tumor lysate-loaded dendritic cell vaccination improves survival in patients with newly diagnosed and recurrent glioblastoma: survival results from a phase 3 trial Plenary Abstract Presenter: Linda M. M. Liau, MD PhD
- University of California, Los Angeles

UCLA Presentaion
DCVax is discussed beginning at minute 40, to focus on Keytruda (pembrolizumab) plus DCVax in combo at UCLA, skip to minute 45:40

Other Relevant Links:

https://www.kcl.ac.uk/people/keyoumars-ashkan

https://www.liverpool.ac.uk/systems-molecular-and-integrative-biology/staff/michael-jenkinson/

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/

https://virtualtrials.org/dcvax.cfm

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

[Dr Bala]

The helmet will be obsolete soon after the DCVax-L therapy becomes the new SOC.

[meirluc]

It is unbelievable that such a post hoc desperately manipulated trial to ends up with such outstanding positive results. Would'nt you say that this is just amazing?
I know that I would.

[LearningEveryTrade]

I don't give a bears crap in the woods about trial not being 'adaptive'. All I care about is the Regulators "Adapted".

[Roman516]

NWBO's Phase 3 trial was in fact adaptive as the trial implied
In addition, since Dr. Linda Liau has previously been involved in what is referred to as adaptative process "TMIC-16. TUMOR-INFILTRATING MYELOID CELLS MEDIATE ADAPTIVE IMMUNE RESISTANCE IN GLIOBLASTOMA"

https://academic.oup.com/neuro-oncology/article/18/suppl_6/vi203/2543434

https://neurotree.org/beta/publications.php?pid=74524

Since the word "adaptive is an adjective", a word belonging to one of the major form classes in any of numerous languages and typically serving as a modifier of a noun to denote a quality of the thing named, to indicate its quantity or extent, or to specify a thing as distinct from something else.
So, the 2018 publication that Dr. Linda Liau does not mention the word adaptive
https://translational-medicine.biomedcentral.com/articles/10.1186/s12967-018-1507-6
However, the adaptive process is in fact implied based on the content of the publication since it includes "denote a quality of the thing named, to indicate its quantity or extent, or to specify a thing as distinct from something else"

Thanks for making this evident once again it supports Dr. Linda Liau and NWBO's effort to make a positive and effective treatment for nGBM and rGBM brain cancer.

[TopelRoad]

I think it has a chance. I would be more confident with gold standard double blind no crossover. But I think it could be approved or approved with confirmatory trial.