NorthWest Biotherapeutics Inc (NWBO)

[Rkmatters]

1)" iRANO is used to account for pseudo progression vs. true progression" -- Reefrad

Your memory is short, we went over this. This trial is determinig patients PFS event based on scans at the time of the visit. Confirmation scans are not being used. They are changing iRANO to account for immunotherapy, based on lessons learned during immunotherapy trials. Only this trial is near the end of enrollment.

Journal of Neuro-Oncology July 2015 addition, within it, is the article written in Feb 2015, "RE-DEFINING RESPONSE AND TREATMENT EFFECTS FOR NEURO-ONCOLOGY IMMUNOTHERAPY TRIALS". Their paper specifically addresses the pseudo-progression in the main arm: "the complexity of radiographic worsening following immunotherapy".

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Immunotherapy responses assessment in neuro-oncology (iRANO) criteria

Although the principals underlying the irRC provide important response assessment guidance for ongoing immunotherapy efforts in general medical oncology, modifications of these criteria appear warranted in order to optimally and safely apply such guidance for neuro-oncology patients. Similarly, although the RANO criteria were drafted to provide more effective assessment of response for euro-oncology patients undergoing therapy in the modern era, RANO alone may not fully address relevant considerations for neuro-oncology patients undergoing immunotherapy treatments. Thus, a multidisciplinary and multi-national group of neuro-oncology experts is currently drafting guidance for response assessments of neuro-oncology patients undergoing immune-based therapies. The immunotherapy response assessment in neuro-oncology (iRANO) criteria will integrate key components of both irRC and RANO in order to take into account important nuances with neuro-oncology patients. A comparison of RANO, irRC and iRANO is summarized in Fig 2. Like irRC, iRANO criteria will also advocate for confirmation of radiographic progression among medical stable patients. However, careful consideration is being included to specify temporal parameters and degree of allowed changes in order to ensure patients safety given potential risk associated with robust immunotherapy changes within the confines of the intracranial space. In addition, iRANO will include guidance for response assessment among patients with either enhancing or non-enhancing tumors. Furthermore, and again in the context of preserving overall patient safety, iRANO will provide guidance on when to consider interrupting administration of an immunotherapy for patients with early radiographic progressive changes. Additional important considerations regarding corticosteroid dosing, the role of advanced MR and PET imaging techniques, the inclusion of metric of neurologic function and overall quality of life, as well as guidance on immunocorrelative parameters to be prioritized in clinical research, will be addressed in the iRANO manuscript. MRI imaging following immunotherapy for neuro-oncolgoy patients, as well as PET imaging approaches suggest that theses modalities may be of benefit in distinguishing tumor recurrence from pseduoprogression. Growing literature also supports the role of MR spectroscopy to predict inflammatory changes from true tumor progression. Monitoring serial assessment over time using advanced imaging techniques may also prove to be particularly helpful rather than single time point assessments.

and:

Conclusions:

Immune-based therapies offer great hope for cancer patients based on their ability to treat existing tumors as well as generate tumor-specific memory immune response capable of preventing future recurrence. Nonetheless, interpretation of early progression radiographic findings has proven challenging in that at least a subset of patients ultimately achieves meaningful anti-tumor benefit. The immuno-oncology community has recently drafted recommendations to guide treating clinicians when confronted with early radiographic worsening that includes continuation of immunotherapy pending confirmation of progression for clinically stable patients. The immunotherapy response assessment for neuro-oncology (iRANO) criteria are currently in development and will integrate key recommendations from RANO with those of irRC in order to help optimally evaluate the therapeutic potential of different immunotherapeutic approaches for near-oncology patients.

I believe that the current halt potentially has something to do with incorporating these new iRANO neuro-oncolgoy changes within the trial. You are free to disagree.

2) "iRANO cannot help if placebo patients are living longer." -- Reefrad

No one is saying iRANO can help if patients are living longer. The idea is to make sure they are not removing patients prematurely from the main arm. And the fact that they may have removed a few means that their primary endpoint took a hit. Adding a co-endpoint will fix that. If regulators allow them to, it's a good thing.

3) "Most of the trial sites do not have access to the newer surgical techniques you mention. They use Stupp and that's it." --Reefrad

I actually did research on it. The first 10 sites that signed up did. Take a look and see for yourself.

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The Company was very strategic on the sites that they added to the study.One of the reasons I bought back in, as I understood that a better surgery means greater chance for success on OS with immunotherapy.

More and more sites are getting the state of the art equipment or do a FGS. And, just so you know, as you probably do not, when NW Bio adds a site, it does not mean that the patient has their surgery there. If you followed the NCT clinical site, you would have seen a specific contact listed at multiple sites. An interested patient might contact someone at let's say Stony Brook Hospital, and end reaching out to someone that works at Long Island Brain Tumor Center at Neurological Surgery, P.C, where they have state of the art diagnostic and surgical equipment.