Replies to post #392780 on NorthWest Biotherapeutics Inc (NWBO)

[Horseb4CarT]

Indeed the same points LL made during one of her presentations several years ago I think. She mentioned the complication/confoundment of the Dcvax data given the trial became early and later application of Dcvax-l, making the often quoted comment that “everyone is living longer.”

I do not think the trial design, changes, and general alignment with evolving FDA thinking is a coinkidink,

[Lykiri]

Thanks ATLnsider!

November 10, 2020
Richard Pazdur, MD, Awarded the Simon M. Shubitz Cancer Prize and Lectureship

Looking to the Future

What might the next 4 decades bring in advances in oncology care?

“Progress in cancer will come from our ability to rely on biomarkers to find cancer before the tumor becomes radiographically detectable. And treatment will center on immunotherapies that activate the immune system to fight this early disease,” said Dr. Pazdur. “I imagine a time when cancer will be detected from a blood test given during patients’ annual physicals, and we will have immunologic drugs that will activate the body’s immunologic defense to eradicate those very early malignant cells. This is my aspirational hope for the future.”

https://ascopost.com/issues/november-10-2020/richard-pazdur-md-awarded-the-simon-m-shubitz-cancer-prize-and-lectureship/

[biosectinvestor]

It would be nice for the FDA to have a successful poster child trial addressing all these issues. Thanks ATL!

[Mionaer1]

Great find. Thanks ATLnsider!

[Mionaer1]

I'm 99.9% sure he's talking about the DC Vax-L study. This means that he was informed about the study at this point and at the same time provides a reason for the SAP change. Namely the mixing of the study participants through the crossover option....

[anders2211]

ATLnsider perhaps you want to respond to this?

https://investorshub.advfn.com/boards/read_msg.aspx?message_id=165228896

[sentiment_stocks]

It's been awhile, but I wanted to review this video more closely. It's very interesting to listen to, and I think his discussion about Project Orbis is especially relevant, as you pointed out, seeing as hopefully sometime in the coming months, Northwest will submit their applications to the various regulatory agencies, and that pathway may prove a means to help speed things up.

Anyhow, regarding Rick Pazdur's speech as it pertained to the randomized trials and cross-overs, it certainly does sound as if he's describing the DCVax-L trial exactly as it was designed. In fact, it's uncanny how closely his description mirrors our trial, but I suppose there are probably other many other trials out there that offered the cross over option as well, although I'm not sure there are very many in oncology.

In the 1980s, after the discussions with the Oncology Advisory Committee, or ODAC, FDA determined that the approval of drugs should be based on improvements in overall survival due to the perception that most oncology drugs at that time had marginal to modest activity with very marked toxicity.

Let’s jump to the new millennium. With the advent of targeted therapies, it became apparent that a reevaluation of the dogma that overall survival was the only acceptable endpoint, that needed simply to be reevaluated.

First, for drugs demonstrating unprecedented response rates in early clinical trials in cancer with few therapeutic options for patients, the ability to randomize patients to either a drug with a markedly improved durable response rate versus a toxic marginally effective drug simply was not feasible… and was of questionable value to either society or scientifically. *Equipoise, a concept in randomization that is inherent in this concept of randomization simply did not exist in many situations.

If a randomized study is conducted in these situations, investigators and patients request a cross over to the investigational drug at the time of progression in those drugs that demonstrated early and forensic (?) activity.

So this request for cross over at the time of disease progression probably represents that true equipoise did not exist in the randomization process. This cross over may confound the demonstration of an improvement in overall survival because patients are basically receiving in both arms the same therapy, albeit, in different sequences.

A demonstration of overall survival may also not be practical in cancers with long, natural histories, due to our advances, or simply due to the long natural history of the disease.

*Equipoise: Clinical equipoise is the assumption that there is not one 'better' intervention present (for either the control or experimental group) during the design of a randomized controlled trial (RCT). A true state of equipoise exists when one has no good basis for a choice between two or more care options.

Clinical equipoise allows investigators to continue a trial until they have enough statistical evidence to convince other experts of the validity of their results, without a loss of ethical integrity on the part of the investigators.