Replies to post #53744 on NorthWest Biotherapeutics Inc (NWBO)

[DoGood_DoWell]

No, one does not have to accept it was a failure, as those who got the better method are showing a better response by immune response and survival from what it appears in the latest charts. It is your choice to believe that or not, and move on if you do.

I am looking forward to the Phase II and the CI combo arm. Good stuff ahead with early glimpses at efficacy likely.

[john1045]

You are speculating and no one knows how the DCVax-L trial is going! I like my odds for success on L reaching primary and secondary endpoints IMO.

The are some posters here who will say all the Direct patients, all Stage IV terminal cancers who are still alive and failed all other treatment regimes, were told to go to palliative care were all cherry picked and healthier than the patients who passed away! I was communicating with Dr. Subbiah early in the Direct trial as I had a friend who was looking for options had Stage III liver cancer but he did qualify for Direct trial.

Do you think Allen Butler was happy to enter the Direct trial with Stage IV pancreatic cancer and Allen is approaching 30 months survival. I guess you will say he was a miracle. Ben Hodges posted here on his wife Laurie who failed 3-4 other treatment options and was told to enter hospice. She entered the Direct trial in February 2014 and recently passed in December 2015 leaving behind her beautiful children and wonderful husband who tirelessly worked to keep her alive. Read Ben's post which Senti posted recently for firsthand knowledge of the Direct trial from patient perspective.

[CherryTree1]

You state:

When the company started touting method A vs method B, I called it total BS. Now the company doesn't even bring it up anymore. I still think that direct was a good try, but one has to accept that it was a failure. Their direction with their p2 IMO will be a waste of time and resources

Why would they still talk about methods A and B. They demonstrated that one method worked and the other didn't, so they abandoned the ineffective method. Have you seen the charts NWBO presented at the Phaciliate Immunotherapy World Forum in January? Look at chart-8 on DCVAX-Direct Ph-1 status update. 12 out of the 36 patents are still alive > 14 months up to 26 months. These are patents with inoperable Sarcoma, Pancreas, Bladder, Melenoma, and Gall Blader Cancers. If Direct works like L works where it is effectively a cure for a subset of the patients, the Mesenchymal subgroup patients we may be seeing the same kind of thing going on for Direct. It is still early, too early to conclude it is ineffective. Lets see if the bulk of the 14 of 26 patients are still alive at 3 and 4 and 5 years, Then we'll know.

[koman]

I guess I did say a lot of things related to NWBO was BS IMO just as some poster stated before the post was deleted. Here is to those who claim that there isn't any evidence that this trial (p3 GBM) is heading towards failure to meet their endpoints. As others and I have already stated many times the various evidence, here is my comment on some of them:

1) preclinical trials show that TLR agonist was required to significantly augment the efficacy of DC vaccines to clear the tumors (cure) in mice. Without TLR agonists, the mice had reduced but still present tumors. The pI trial used TLR agonist to show very promising data. This p3 trial is not using TLR agonist. Flipper claims that this trial protocol can compensate for the lack of use of TLR agonist but there is no pI data from NWBO or UCLA that shows comparable results.

2) Dr. Liau's Oct 2015 comment that all patients are living longer if taken out of context as many longs are doing as a sign of these patients living much longer than SOC is problematic. Why? Because the UCLA pI trials that tested the DCVAX-L on rGBM patients showed a medOS of 17.9mths FROM INITIAL DIAGNOSIS. (post 4630 on IVil) This is data from the pooled 14 rGBM patients. These are patients that will closely represent the placebo cross-over grp in the p3 trial. DCVAX-L did not enhance their OS beyond the range expected for nGBM. Interesting to note though that the 2 rGBM treated with TLR agonist lived beyond the medOS. The rest of the rGBM patients for whatever reason did not receive TLR agonists which allowed me to use that data to get a peek at how the placebo cross-over grp might be doing. So if Dr. Liau claiming that the cross-over effect is not helping their trial, then this is a major problem if the placebo cross-over grp can't even reach the upper end of the range for what can be seen for these patients. I'll spell it out for you. That would indicate that the DCVAX-L arm isn't doing much better than the 17.9medOS. I would have hoped that the medOS for both grp would have reached at least 24mths but the previous data doesn't support that hope.

3) Concerning DIRECT: I enjoyed hopefulsurgeon's post. I sincerely hope that there will be better arsenal for surgeons like him be available to treat their cancer patients to extend lives beyond just palliative effects and potentially cure the cancer or at least have a long durable response. Here is a paper from a Japanese grp that did a intratumoral MATURE DC injection in a patient with Gastric metastasized Cancer where he was "cured" or had a CR that was durable. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4320508/
World J Surg Oncol. 2014; 12: 390.
Published online 2014 Dec 19. doi: 10.1186/1477-7819-12-390
PMCID: PMC4320508
Therapeutic effect of intratumoral injections of dendritic cells for locally recurrent gastric cancer: a case report

This was what I was hoping for from the Direct pI trial. Note that this Japanese grp believes that the problems other labs had was that they used IMMATURE DC. This is up for debate and this one successful case report may be just an isolated rare case but at least they had one and DIRECT has so far shown ZERO CR or even PR. Maybe method B just ain't "better" enough.

So to settle for showing increasing Necrosis is a true disappointment to me at least. Here is another paper that correlates Necrosis to clinical outcome: http://annonc.oxfordjournals.org/content/15/5/775.full
Induction of complete tumor necrosis may reduce intrahepatic metastasis and prolong survival in patients with hepatocellular carcinoma undergoing locoregional therapy: a prospective study

It took a COMPLETE tumor necrosis to correlate to extended survival. What was the extent of tumor necrosis induced by DIRECT? I don't think they even showed one patient with 100% complete tumor necrosis but I could be wrong. This grp showed 39% of their patients having complete tumor necrosis using ACETIC ACID as part of the injection protocol. So I would hope that any future attempts at using the expensive DC won't try to achieve complete tummor necrosis as its goal but rather try to achieve the elusive PR and CR that CI have shown or at least a DURABLE SD.

4) Also, since it appears that UCLA is running the stealth p2 combo trial, Dr. Liau is getting a peek at data that has relevance to this blinded p3 trial. I would hope she shares that data with the rest of the world soon.