Replies to post #516510 on NorthWest Biotherapeutics Inc (NWBO)

[hoffmann6383]

LOL, why would nwbo waste time talking about bullshit that you only see peddled anonymously. federal judge already shot that crap down

have a good one chrissy!

[SkyLimit2022]

Thank you for again highlighting the exemplary design of the innovative, compassionate, and clinically appropriate P3 that is often misunderstood. The FDA, the P3 investigators, and others have recently spoken on this topic.

“Crossover was necessary for feasibility and ethical reasons:

—Necessary for enrollment and retention of patients in an era when immune therapies are not yet generally viewed as promising for cancer

—Important to justify all patients undergoing invasive leukapheresis procedure

—No benefit to placebo patients unless they could receive their autologous product made from the leukapheresis”

"Often, novel agents are so obviously superior to standard of care that no patient would participate in a randomized trial knowing that somebody else might get the experimental drug”—Richard Pazdur, MD

Richard Pazdur, M.D. is the director of the FDA's Oncology Center of Excellence (OCE), which leverages the combined skills of the FDA's regulatory scientists and reviewers with expertise in drugs, biologics and devices to expedite the development of novel cancer products. In his role as director of the OCE, Pazdur is responsible for leading the effort to develop and execute an integrated regulatory approach to enhance the cross-center coordination of oncology product clinical review.

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

OS is the gold standard and was always an endpoint.

Anyone can research for themselves 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.”

The landmark trial was a brilliant success and the independent peer review is forthcoming.

Dr. Linda Liau is a world-renowned neuro-oncologist, surgeon, and educator at UCLA where she is also the chair of the department of neurosurgery. As her paper on DCVax moves through the independent peer review process, it is interesting to note that she was once the editor-in-chief of a neuro-oncology medical journal.

https://www.uclahealth.org/providers/linda-liau

https://doi.org/10.3171/2020.12.FOCUS20954

https://soc-neuro-onc.org/

Across the pond from Dr. Liau, Dr. Ashkan was the chief investigator of the DCVax trial for patients in Europe. At King’s College in London, Ashkan is the lead clinician for neuro-oncology and the chair of the King’s Neurosciences Clinical Trial Unit. He is a world-renowned cancer trial expert. A few years ago, Professor Ashkan was named the UK Clinician of the Year by The Brain Tumour Charity. Additionally, Ashkan serves as an advisor to the U.K. government.

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

Most recent news and events:

https://connect.uclahealth.org/2022/09/14/brain-cancer-discovery-clinical-trials/

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

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

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.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

[meirluc]

I would take a post hoc, so called data dredged rGBM endpoint any time if that endpoint includes an mOS that is more than 8 months longer than that of the
ECAs. I would also like to understand the procedures that could be used by NWBO to data dredge the trial and placebo arm in a way that would result in 64 crossover patients whose mOS is north of 24 months.