GET READY we are NOW GETTING CLOSE
I reviewed my prior dataset and assumptions; Any amount of time that elapses without discloser of achieving the 248th event, After the beginning of Aug 2016 is golden and represents treatment efficacy and significant treatment effect.
Please review my prior posts. In Nov 2016 we will nearly 4 months from when the expected number of events should have occurred based upon SOC.
POST 47777
Significant PFS improvement and Time Analysis for DCVax-L GBM trial
To better understand this post and my model, Please reference my prior posts regarding modeling for the DCVax-L GBM trial.
IHUB POST 3433 uses the STUPP trial as the Model for the control patients.
IHUB POST 14585 used the IMUC data to further refine the model data.
IHUB POST 17001 from Flipper
FIRST Things we know ... Dec 2013 there were 66 events disclosed prior to the trial being expanded. We know the published STUPP and IMUC Control and Treated patients progression free survival (PFS) curves.
Furthermore, recently it was disclosed in August 2015 that the DCVax-L trial had accrued 300 patients randomized. This discloser gives us the average accrual rate for the trial from Dec 2013 to August 2015.
Using the above data, I then proposed the following model and thought experiment.
For the purpose of this model analysis, we make the following assumptions. Let us pretend that after the trial was expanded in Aug 2014, increasing the N to 348, that the experimental DCVax-L treated patients and non-treated, all had exactly the same progression free survival PFS, as did the control patients from the known STUPP and IMUC trials.
Using these parameters, our model would then provide us a worst case scenario in terms of when the number of events in the DCVax-L Trial would occur to give us 148 events, (first interim Analysis), 198 events (second interim analysis), and 248 events (Trial end). When one models the data in this manner, one obtains the following results.
The 149th event would have occurred in June 2015, and the 198th event would occur in Feb 2016 and the 248th event would occur on August 2016.
Therefore each month that passes after June 2015 without any announcement that the first interim analysis (148 events) has been reached, indicates that during this time period there have been less events than what would have been expected, had the patients progressed in a manner similar to the control groups from the STUPP or IMUC randomized trials. Less events means that the DCVax-L treated patients have survived longer without any progression, then what would have been expected by these control groups.
Therefore, each month that there is no announcement provides further evidence that the DCVac-L trial will yield a positive significant result favoring the dendritic treatment.
Discloser: I am long this stock and I am a smart clinical researcher whose hobby is to model survival data with complex statistical software
POST 14585
Updated from prior post and new IMUC Data.
Discloser: I am long this stock; I have no inside information; I am a clinical researcher.
Hypothesis 1: The Control Patients in the DCVax-L GBM trial should relapse at a rate similar to what was shown in the IMUC trial. The IMUC trial is the most similar to the DCVax-L GBM trial in terms of eligibility entry criteria. The progression free survival (PFS) was reported recently at the 2014 American Society of Clinical Oncology (ASCO) meeting. In order to compare the IMUC Trial to the current DCVax-L trial control patients, however, one must add 83 days to the IMUC results because the IMUC data time 0 for PFS was upon first administration of immunotherapy (ie after surgery and RT) whereas the DCVax-L Trial (and every other major trial in this disease) calculated the start day 0 for the PFS curves at the date of surgery. The Median PFS for the control patients in the IMUC trial was 9 months. When one adds the 83 days to this on gets 11.72 months median PFS for the control patients in the IMUC trial. Therefore the control patients in the DCVax-L trial should be around 11.72 months. (And to be conservative I used 12 months median PFS for this modeling.
Hypothesis 2: Given that we know the number of events in the total DCVax-L trial at this time (first interim analysis) is 67, then one can model using JMP(SAS) software, the control arm PFS to be similar to the corrected IMUC trial results and thus obtain an estimate for the probable number of events required in the control arm of the DCVax-L trial to give a 12 month median PFS at the first interim analysis date (Mid Dec 2013). When one does this with a Kaplan Meier plot, one obtains a result of a minimum of 25 (Max-Min; 28-25) events in the control arm with the total number of patients in the control arm of 57. Then one can deduce that the number of events in the experimental arm for the DCVax-L trial would be 67- 25 or 42 events. I used the minimum events in the control arm be conservative and get the maximum potential number of events for the experimental arm.
Hypothesis 3: Using the derived 42 events in the experimental arm, one can model the experimental arm to be similar to the IMUC trial results but, in this case only allow for just 44 events out of 114 total patients in the DCVax-L experimental arm. When one does this with a Kaplan Meier plot, the median PFS for the experimental arm returns > 17.763 month median PFS in the DCVax-L experimental arm. When one applies log-rank and Wilcoxon significance testing to the two curves one obtains a significant result of p=.0364 and a nonsignificant but trending p =.0781 respectively.
My best educated guess is that the DCVax-L trial is going to return a positive result on the primary end point but this is now a much closer horse race. I suspect that analysis such as this has caused NWBO to consider increasing the total N for the trial in order to give a higher probability for obtaining a significant result. Hence the delay until 2015 for study closure which was recently reported.
This however will still be a practice changing result. Just to put this into perspective the Stupp GMB trial PFS only increased 2 months by the addition of temazolamide (TMZ) (5 to 6.9 months). Yet this became almost immediately, the new gold standard of care in this disease and TMZ almost immediately became a blockbuster muli-billion dollar drug.
DCVaX-L increases in the operable patients even more than this and will be the new standard of care in this disease.
