NorthWest Biotherapeutics Inc (NWBO)

[SkyLimit2022]

Thank you for reposting that again tonight. I believe it is advisable to wait for the independent peer-review. Licensed independent physicians and qualified skilled statisticians will explain the significance of this landmark trial, its design, and its data. Avoid social media disinformation and anonymous message board postings.



As always, we appreciate your opinions about DCVax. We also value the ideas of investors in competing technologies. We like to hear from all sides and never mind seeing repetitive reposts. It’s always good to review and refocus and consider important points more than just one time. I would add that the opinions of licensed oncologists are valuable too and we must be careful to avoid disinformation about medical topics posted online. Please do your own research and consult licensed professionals and trustworthy sources.



Please review some of the links below. I believe you will discover that FDA-NIH has consistently supported DCVax and approved DCVax clinical trials including the current Keytruda combo study at UCLA which is also funded by Merck.

OS is the gold standard. Research this fact to verify it and to get greater context and a more clear understanding: PFS is a surrogate for OS and only used because its data are 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.

Most recent news and events:

https://m.youtube.com/watch?v=h_tev1qm1ZE&feature=youtu.be
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.

https://youtu.be/Oq39FFUwKug
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

Yes, you are correct that the FDA is crucial and I certainly would agree with that. The U.S. government (FDA-NIH NCI) is largely responsible for the development of the DCVax platform technology as they have always supported and funded Liau’s work. The 20 consecutive years of NIH funding of Dr. Liau have played a direct and crucial role in DCVax. Together with Merck, NIH is funding the DCVax doses going into arms TODAY in a study investigating its efficacy in combo with Keytruda.

FDA has approved multiple DCVax trials and their design including the ongoing Keytruda trial.

September 14, 2022 Update of NIH NCI Funding of Dr. Liau

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

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

https://www.bentley.edu/news/nih-funded-research-related-every-new-cancer-drug-approved-2010-2016

9/14/2022
In a trial now underway, a dendritic cell vaccine is made from a participant's own tumor tissue and combined with an anti-PD1 immune checkpoint inhibitor to counter resistance when either treatment is used alone. The checkpoint drugs work by blocking the proteins that stop the immune system from attacking cancer cells.

"What I'm excited about is that we're seeing a growing number of long-term survivors in our patients treated with immunotherapy combinations," Dr. Liau says. "We're seeing some patients with certain combination immunotherapies that are living for many more years than would be expected. Currently, we're trying to find out what combination works best and for which patients."

https://cancer.ucla.edu/research/ucla-brain-spore

https://www.merck.com/stories/fighting-cancer-requires-an-open-mind/

Merck: “Personalized cancer vaccines which are therapeutic vaccines based on patients’ specific cancer that could potentially prime the immune system to recognize certain characteristics and attack the cancer cells”

https://m.youtube.com/watch?v=Oq39FFUwKug

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

NCI, Merck, & PHASE ONE are today supporting collaborators on the UCLA Keytruda trial—100% of patients in both the experimental group AND the placebo group receive DCVax. Only Keytruda in combo is being investigated—everyone receives DCVax as if it were SOC.

Group A (pembrolizumab, ATL-DC, poly ICLC)
Beginning 14 days prior to scheduled surgery, patients receive pembrolizumab IV over 30 minutes. After surgery, patients receive pembrolizumab IV over 30 minutes on day 1. Cycle repeats every 3 weeks in the absence of disease progression or unacceptable toxicity. Patients also receive ATL-DC ID with poly ICLC IM every 2 weeks for up to 3 doses in the absence of disease progression or unacceptable toxicity.

Group B (placebo, ATL-DC, poly ICLC)
Beginning 14 days prior to scheduled surgery, patients receive placebo IV. After surgery, patients receive placebo IV on day 1. Cycle repeats every 3 weeks in the absence of disease progression or unacceptable toxicity. Patients also receive ATL-DC ID with poly ICLC IM every 2 weeks for up to 3 doses in the absence of disease progression or unacceptable toxicity.

https://clinicaltrials.gov/ct2/show/NCT04201873

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/



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

https://m.youtube.com/watch?v=h_tev1qm1ZE&feature=youtu.be

https://virtualtrials.org/dcvax.cfm

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.

Pazdur has published more than 400 articles, book chapters and abstracts. In 2015, Fortune magazine named Pazdur as one of the 50 World’s Greatest Leaders. The American Association for Cancer Research recognized Pazdur with its Distinguished Public Service Award (2015) and the American Society of Clinical Oncology recognized him with the Service Recognition Award (2009) and the Public Service Award (2013). In 2015, Pazdur also received the Public Service Leadership Award from the National Coalition for Cancer Survivorship and also the Face of Hope Award from the LUNGevity Foundation. Most recently, in 2016, Pazdur was named to Massachusetts General Hospital Cancer Center’s “The One Hundred” list.

"Now we are in the era of immunotherapy"
-Richard Pazdur, MD

"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

"There's also been a revolution in tumor immunology. Before, in my early career, tumor immunology was looked at kind of as black magic, as witchcraft. Now it's accepted."
-Richard Pazdur, MD

"When we make a decision about approving a drug, it has to be patient centered. It can't be about the regulations"
-Richard Pazdur, MD

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

https://www.fda.gov/drugs/news-events-human-drugs/50-years-progress-treating-patients-cancer

https://www.webmd.com/cancer/cancer-in-context/video/richard-pazdur

https://www.onclive.com/view/pazdur-followed-the-pathway-of-greatest-resistance-to-the-fda

So many of these survivor stories are old news— research 2022 updates—some are GBM patients surpassing a decade or multiple decades—miraculous …

https://www.hawaii.edu/news/2017/03/30/newirth-laker-for-a-day/

https://m.youtube.com/watch?v=K9azZaIwOH8&feature=youtu.be

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