Replies to post #787368 on NorthWest Biotherapeutics Inc (NWBO)

[seekinganswers]

The original endpoint (gold standard) for DCVax was PFS.. It failed, (they knew it) then they changed the endpoint to OS, and THEN splattered coffee all across the trial results with crossover and THEN added phony external controls. COMPLETE DISASTER! IMO.

DCVax Original Endpoint in Clinical TrialsDCVax refers to a family of investigational personalized dendritic cell vaccines developed by Northwest Biotherapeutics for treating solid tumors, particularly glioblastoma multiforme (GBM), an aggressive form of brain cancer. The most prominent trial is the Phase 3 study of DCVax-L (autologous tumor lysate-loaded dendritic cell vaccine) for newly diagnosed and recurrent GBM, registered under ClinicalTrials.gov Identifier NCT00045968. This trial, which enrolled patients starting around 2007 and completed enrollment in 2015, initially used a randomized, double-blind, placebo-controlled design. Below, I'll outline the original endpoints based on the trial's prospective design, drawing from publications and trial descriptions.Original Primary EndpointProgression-Free Survival (PFS): The primary endpoint was PFS, defined as the time from randomization to disease progression (assessed via imaging using criteria like RECIST or RANO for brain tumors) or death from any cause. This was intended to evaluate how effectively DCVax-L delayed tumor progression when added to standard-of-care therapy (surgery, radiation, and temozolomide chemotherapy).In the interim blinded data reported in 2018 (from a subset of patients), median PFS was approximately 6.2 months in the DCVax-L arm versus 7.6 months in the placebo arm, which was not statistically significant (P = 0.47). This led to the trial not meeting its original primary endpoint in the prospectively defined analysis.
PFS was chosen as the gold standard primary endpoint in oncology trials like this one because it provides an earlier readout than overall survival (OS) and is less confounded by post-progression treatments in GBM, where subsequent therapies are common.

[brooktrail1933]

"palls" (sic) "pals"

"summery data" (sic) "summary"

People who cannot spell cannot be taken seriously.

[skitahoe]

Ex, there is no doubt that when the trial began PFS was the desired path to approval. The problem was pseudoprogression which made PFS an invalid measure. The regulators agreed with the company that the trial could proceed with OS as the goal. OS had previously been one of the goals, but it became primary when patients were deemed to have progressed when in reality they were greatly improving, the cancer appeared bigger but in reality, was dead matter, not an actively growing cancer.

There was a time that regulators wouldn't have supported such a change, they'd have said end the trial and start a new one designed to consider pseudoprogression. Fortunately, the regulators have evolved and trial design can be reconsidered based on what's being found in the trial.

Gary

[sentiment_stocks]

So then is the 13% five year survival rate for GBM patients in the treatment arm a joke to you, and your friends?
Especially when around 60% of the GBM patients in the DCVax-L trial were unmethylated.

Median survival rate of eight months; 5-year survival rate of 6.8%
https://braintumor.org/brain-tumors/about-brain-tumors/brain-tumor-types/astrocytoma/#glioblastoma

Anybody with a clue in this space knows that is a JOKE. - exwannabe

And how about the 13.2 mOS of the recurrent GBM patients in the DCVax trial? Is that a joke to you and your buddies too?

Most GBM recurs in 6 to 9 months and the median OS since recurrence is 3 to 9 months. Despite advancements in clinical trials, there is no uniform standard of care (SOC) for recurrent GBM.
https://ascopubs.org/doi/10.1200/JCO.2023.41.16_suppl.e14057#:~:text=Abstract-,e14057,(SOC)%20for%20recurrent%20GBM.

Those OS stats are facts that the regulators are not going to ignore.