Replies to post #591248 on NorthWest Biotherapeutics Inc (NWBO)

[HappyLibrarian]

Tossing out primary endpoint that failed when a trial is virtually complete is very suspect for ANY trial. Ya think the FDA has seen every failed trial be spun into something that looks good. They will not look kindly on NWBO's protocol spin.

Ordinarily you would be right but Optune while better than nothing, does not provide enough benefits and SOC is a sick joke.

There will be a lot of pressure to not put off the chance of an effective treatment by another decade. Think about the approval FDA did for Alzheimer’s despite significant doubts.

While it is a technical fail that we should not gloss over, it is still worth noting that PFS is meant to be a surrogate for OS to shorten the length of the trial. NWBO already had to pay a penalty in time for switching to OS because DCVax-L was too effective and patients took too long to event and do the trial went on and on (good for the individuals but bad for getting the trial done and getting life extension to more patients years earlier).

Being a bureaucrat myself I can assure you that we are willing to make things happen fast in exigency circumstances and ignore technicalities are very good at dressing it up with the best of paperwork.

Could regulators fail DCVax-L? Yes it’s a 5 to 10 percent chance (this factors in conspiracy theories about BP and regulatory capture.

But will they?

No, I am going with the 90% to 95% chance.

[SkyLimit2022]

HyGro,

Your assertions are verifiably false. PFS did not not fail as subsequently proven by the OS data. The PFS data were contaminated and therefore the investigators could not use the inaccurate PFS data as a reliable surrogate predictor of OS. Instead, they had to wait for actual OS data.

Oncologists always attempt to measure and predict PFS as they should.

OS is the ultimate standard, but you cannot wait until death to begin evaluating whether a cancer drug is efficacious. The physician must evaluate a patient’s response and try to determine whether the treatment is helping.

Today, doctors have better methods for measuring progression, particularly when studying immunotherapy agents which are still relatively new as the emerging field of cell-based science is leading to rapid changes in the understanding of how cancer can be assessed and treated.

The P3 for the DCVax-L cell-based technology spanned many years. If the trial were designed and commenced in 2023, the investigators would appropriately attempt to measure progression and predict survival using the best methods and most current medical knowledge available in 2023, as any cancer researcher would.

Interview with Linda M. Liau, MD, PhD, author of Association of Autologous Tumor Lysate-Loaded Dendritic Cell Vaccination With Extension of Survival Among Patients With Newly Diagnosed and Recurrent Glioblastoma, in a podcast with @JackWestMD. https://t.co/POEeEg5cVz

— JAMA Oncology (@JAMAOnc) November 18, 2022

This study found that autologous tumor lystate-loaded dendritic cell vaccination plus standard of care (SOC) was associated with improved survival in both newly diagnosed & recurrent glioblastoma compared with matched controls who received SOC treatment. https://t.co/Uso7Pkh1Kt

— JAMA Oncology (@JAMAOnc) February 15, 2023

https://brownneurosurgery.com/breakthrough-brain-cancer-vaccine/




Thank you for mentioning the PD1 trial:

https://investorshub.advfn.com/boards/read_msg.aspx?message_id=171752448

[skitahoe]

I wasn't an investor back at the time of the halt, I think that was 2015, believe it or not, that's when PFS was abandoned as a goal with the concurrence of the regulators. Coming out of that halt it was clear the control group was abandoned and so was PFS, everyone knew of pseudoprogression back then and they agreed to change the trial protocol. Nothing required these changes to immediately be made in clinical trials, or anywhere else, nor did an SAP need to be agreed on immediately, it only had to be done before the trial was locked and the data collected.

I don't doubt that things like getting all four regulators to agree on things like the SAP may have taken much longer than people believed it would, but again the only deadline was do it before the trial was locked. I suspect that the company and the regulators may have agreed that 5 years of data for even the last patient to enter the trials was desirable, but only they can say if it was agreed on, or if the company determined to take it that far, or further to get a specific number of events.

You can keep repeating your opinion that these changes were made after they knew the data, it's clear this isn't the case, the decisions were made back when things changed during the halt. The trial resumed with all receiving the vaccine and pseudoprogression clearly determined to have falsely been thought to be progression.

Believe what you will but you cannot deny the changes made after the halt and those changes all support how the trial was ultimately documented when the documentation was changed, and all that needed to be changed before the trial was locked up had been changed.

Gary

[Roman516]

Who cares is correct.

Per your comments
"Who cares. What matters is NWBO designated PFS as their primary endpoint and the trial FAILED to meet the endpoint and they tossed it out. Dr. Liau designated PFS as the top efficacy measure in her Keytruda combo trial, so the argument that DCVax-L causes pseudo-PFS seems specious or she certainly wouldn't use it. Previous GBM trials have shown many treatments also can cause pseudo PFS but PFS is a commonly used metric. Again just look at Dr. Liau's protocol.

Tossing out primary endpoint that failed when a trial is virtually complete is very suspect for ANY trial. Ya think the FDA has seen every failed trial be spun into something that looks good. They will not look kindly on NWBO's protocol spin."

The fact remains that the OS data results outperformed the PFS, "The statistical guess factor results."
You already know this, but it is worth repeating. The OS data is the gold standard and that is the bottom-line FACT.

[Dr Bala]

Need to post on the low glioma trials. That would be of benefit to us. Post on the INDIGO trial. Good lines on PFS too. Ignore the OS. Low glioma trials will increase the knowledge.