1) "I wanted no risk" That's what I thought, your choice of dates was influenced by the outcome you wanted to find. If you used a more reasonable later date then it would indeed be harder to demonstrate rintega's efficacy.
2) "You should learn the curves of the EGFRVIII population" If you are privy to more recent trials that show survival curves please share them. In the meantime I will go with what CLDX found by mining data from the largest GBM trial to date: for pts best matched to those in ACT IV, the 3 year survival for standard therapy was 13%. Those survival curves must be pretty wacky to also have survival at 5 months prior only 5%. Zombies?
3) You ignored my point. Patients are screened and enrolled during the chemoradiation portion of their treatment. Only later do they start maintenance TMZ and rindo. The only way your 3 months is applicable is if pts were screened, enrolled, and treated on the same day.
Those are interesting facts about NWBO and MGMT but, of course, have nothing to do with the topic.
Not bad, but if you were to put error bars on all the assumptions you have to make the conclusion would not be so definitive (especially 92%!) Some other concerns:
1. "For group A the Median Start Date is ~Jan 2013" Looks you just use a linear rate of accrual here. Centers usually start slowly and then pick up in accrual rate. Plus the first patient wasn't screened until December 2011. The average of dates in the first group is January 2012; the mean is probably later.
2. " Expected % of events in group A : 95%" That is lower than what CLDX has found after looking at the large study of dose-dense TMZ. For the patients in that study that match the entry requirements in ACT IV, the OS at 36 months was 13%. for all v3 pts, even including those with less resection or died soon after diagnosis the number is suprisingly larger at 18%. Why did you use 5% at 31 months?
3. "since trial start date + 3 months after Diagnosis and resection" Yes, 3 months typically after diagnosis/resection but patients were screened/enrolled (the median date you provide) in the interim period, not the day they start Rindo treatment.
Even if you believe the numbers are all accurate, you are assigning ALL of the extra survival to the treatment arm. rindo has been studied in quite a few people over many years and the 22 month survival has been pretty constant. Survival of patients outside of those receiving rindo, howver, has been trending upwards.
the ucla neuro-oncologist behind the NWBO treatment caused a stir recently when she let slip that a lot of GBM patients are doing well in the trial suggesting the control group is living longer than expected. Might you have found the same thing?
"The ACT IV log is published online"
I really feel out-of-the-loop. What are they logging and where online?
This guy has been around for a long time under several aliases.
Initially he was angry because I ignored his silly questions. Now he is angry because I comment on his silly posts.
The 2011 study of the role of EGFRvIII in glioblastoma patients in Rome found results that should have been a warning: mean OS = 19 months for patients with EGFRvIII(+) tumors, significantly LONGER than patients without v3+ tumors.
Remember the boast that rindo was eliminating EGFRvIII in 80% of the recurrent tumors? For these patients in Rome "relative to GBMs at primary surgery, the level of EGFRvIII in the recurrent tumors decreased by approximately 50%on average".
Montano etal Expression of EGFRvIII in Glioblastoma: Prognostic Significance Revisited
I'll just say this: At these price levels CLDX has almost turned into a value stock. Consider that they paid about $40 million for glemba when there was much more uncertainty about its activity, and we know that BMS was willing to pay millions just for the right to exclusively test its PD1 antibody with CD27. Also look at the upfront payments for partnerships in the immunotherapy space.
Somebody tell Biden not to waste money searching for a cure, CLDX is already there?
I wonder why the trial was not stopped at the first interim analysis in that case.
"You shouldn't get involved with bio stocks if you don't practice it."
Probably true, though I'm here mainly for the social aspects.
So by log you mean the list of changes to the trial. From that you guess (extrapolate) the enrollment over time from the numbers of centers recruiting (patient's enrollment progress to the more practiced.) Your numbers actually match up well with the limited enrollment numbers CLDX has given us.
I'll add some more comments to your original thread.
Just as with the much-discussed stopping for efficacy parameters, the cut-off to stop for futility is always much more strict at the first look. I don't know the actual numbers, usually it requires a clear sign the treatment is worse than the control. If about the same, as the case here, trial continues.
Glad you agree. A lot of folks here seem to think that Duke would want to showcase some work at their lab from more than 10 years ago instead of the newer stuff they are working on now that would actually benefit from the increase in research funds that Biden proposes.
" quite dramatic effects" from PII varli+ checkpoint inhibitor (Nivo)
When did anybody say that? Are they sending you coded messages again?
"if trial goes forward to Nov, high probability because p value less stringent "
Need parantheses around high probablity.
"it shows a level of poor management that is hard to believe"
Wasn't the lack of partnering considered a good thing on this board just a couple of weeks ago? Because the programs are wholly-owned the launch of the share price could go to the moon.
BTW, they partnered with Pfizer after the Avant/CLDX merger.
Some of Sampson's recent papers in glioblastoma that may have been the "cutting-edge" research discussed:
1. Oncolytic polio virotherapy of cancer. Cancer. 2014;120:3277-3286.
2. ntracerebral delivery of a third generation EGFRvIII-specific chimeric antigen receptor is efficacious against human glioma. Journal of Clinical Neuroscience. 2014;21:189-190
3, EGFRvIII mCAR-modified T-cell therapy cures mice with established intracerebral glioma and generates host immunity against tumor-antigen loss.Clinical cancer research : an official journal of the American Association for Cancer Research. 2014;20:972-984.
4. Tetanus toxoid and CCL3 improve dendritic cell vaccines in mice and glioblastoma patients 2015 Nature
COMBINATION OF ANTITUMOR IMMUNOTHERAPY TARGETED AGAINST CYTOMEGALOVIRUS (CMV) PLUS REGULATORY T-CELL INHIBITION IN PATIENTS WITH NEWLY-DIAGNOSED GLIOBLASTOMA MULTIFORME (GBM) 2015 Nature
Even if the trial is successful in the primary population, near total resection, a lot of the market opportunity is
Multifocal and bulk disease. Most cases are tougher than those eligible for the trial.
You also need to factor in that rindo would be stopped at progression. Median pfs in ACT III was only 9 months.
"...but that is why it was spun off."
Medarex knew that they would get better offers without the technology that was transferred to CLDX?
Possibly true. FOUR YEARS before the buyout of Medarex they spun out the speculative APC technology that has brought us CDX-1307 (remember that one- the trial was stopped before it started) and CDX-1401. not too long prior to that event they signed a development deal with BMS, but were not talking buyout yet.
May want to reread those pr's - it was not compared to chemo. Both the control arm without the vaccine and the Rintega arm received standard very toxic chemo therapy and radiation.
Furthermore, the treatment did not work at all compared to the control.
Indeed true, but if you have a loss in CLDX likely better to harvest it at the time of the buyout by selling than just letting sit in the new basis for the acquirors stock you will receive. If you sell and then buy the buyer you get both tax loss and the possible stock appreciation.
"My husband has been on the Celldex trial since May of 2013- He is doing very well and tumor continues to shrink.--Laura"
"My husband's last MRI showed an indication of a new tumor growth in a differnt location. This means that he has been kicked off the Celldex trial. They are starting my husband on the DCVax -L."
Laura ..... On Friday, January 8th 2016 - RB left this world with strength, grace, and class.
She was diagnosed January of 2013 with GBM.
My mom had her first reoccurance in August of 2015
"I am currently in the trial. Have been for 6 months. For me it's double blind but my NO and I are suspecting I'm getting the vaccine. My last MRI appeared to show the tumor shrinking."
"I am in the DCVax-L trial and my tumor has shrunk and gone into maintenance. Great trial."
--ezed (his other messages do sound like it is the rindo trial though)
All seem convinced it is the active drug. Selection effect or evidence of long PFS in the control arm?
Celldex has also traded for at just the cash value - right after the merger with Curagen.
In many ways, Celldex today is more Curagen than CLDX - Curagen shareholders received more than 50% of the shares and now the lead product is a former Curagen product.
"Vice President Joe Biden, charged by President Barack Obama to lead government efforts to find a cure for cancer, will discuss his plans next Wednesday at the Duke University School of Medicine, his office said.
Vice President Joe Biden, charged by President Barack Obama to lead government efforts to find a cure for cancer, will discuss his plans next Wednesday at the Duke University School of Medicine, his office said."
If these cancer cures envisioned by Biden are successful it would be bad news for CLDX products, no?