I gave a call to Cel Sci today (Same post on Yahoo MB)
I was lucky enough to be able to talk to Dr Talor and he has kindly offered to answer some of my questions.
So I am happy to share with the community today with the best of my understanding and my own words, sorry M. Talor if the wording is not as precise as it should be.
First of all he confirmed that despite the study was open labelled they were completely blinded.
He said IDMC should meet in general every 6 months, provided that there is enough to be discussed /analysed between two meetings.
Regarding 3 Years survival, he said that the nature of the tumor being treated (most in % is dealing with oral cavity) plus the staging (Inclusion criteria) made it eligible for the low-end survival numbers for Head and Neck cancer (in general H&N survival statistics given in literature talk about relative survival for a blend of lips, tongue, soft palate etc…which is better then what it should be from this Clinical Trial). He confirmed again that 298 includes all kind of deaths, therefore survivors are “overall survivors” and not “relative survivors”
He said :
- Survival hope at 3 years has not increased much for this specific cancer location over the years
- HPV do not impact much this zone of the mouth and therefore should not influence survival either
- No chance than Checkpoint inhibitors have had time to improve SOC from 2011 to 2016 in particular in the regions where the CT took place
He said dropouts should be contained as no more patients than the initial design were required to get statistical significance
Having all this in mind, he said that the fact that most of patients have been treated more than 3years ago (some more than 7 years) and 298 not being reached shows a survival pattern that is in not in accordance with what should be expected from SoC alone. (Personal note : This point is the main evidence given by the models that we have run so far that tend to prove that the drug is efficient)
On the question of Primary Endpoint : he said it was Event driven and not Time driven (as I suspected). They have to wait for 298 and then they compare survival in two arms and there is the need to show 10% Overall Survival improvement in MK arm. Average 3 years simply means the time they though 298 would be reached when they designed the study. Timeframe is required for Secondary endpoints such as Progression free survival, QoL etc…
Finally on the question on why this Science would work while every research seems to focus on Treg inhibidors : he simply said because he saw it work on more than 200 cases in prior studies ! He said that the fact that they treat prior SoC on an intact immune system without delaying SoC is a key point in the success of the drug that is being considered seriously now by some research oncologist and should be an eye opening if CT is successful.
Bottom line and my personal conclusion :
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All the models ran so fast, based on time it takes to reach 298 event indicate that there is some efficacy shown in the MK arm. Most models show a strong efficacy over 10%. This discussion with Dr Talor only reinforces this feeling as it emphasizes the fact that survival expectancy is still poor for this category of patients treated with SoC.
I hope my transcript is a faithful reflection of what has been discussed, overall, do your own DD, make your own decisions.
Fosco
