Doc,
Let's say no IA was conducted in August, but instead the company is simply trying to change the study to give it the best odds of PFS endpoint success. Remember they already know that pseudos wreak havoc on trials. It is not "head in the sand" thinking that the company isn't trying to use whatever advantages it can to de-risk the trial. They already did it using the WBC and in that instance, I truly believe they were able to get their manufacturing patent to pass. In this current situation, I imagine it as the same, but instead their armed with new iRANO to support their request for a change. By allowing the study to use proper imaging techniques suitable for immunotherapy trial to determine the primary endpoint success to me is the right thing to do. It's the smart thing to do. The regulators easily may have adopted a watch and see approach before deciding on this one too. Perhaps they want to see some questionable MRIs and will watch those patients after PFS. Typically within 7 months after progression patients pass. If that's not the case with DCVax-L, maybe it is the vaccine affecting the difference.
My view is the findings will support it is helping patients on overall survival live longer lives than they may have otherwise had without it. Whether it is making a significant difference, I do not know. But my guess is that there will be a decent percentage of long-tail survivors in this study. Upon progression, even a false one, the breaks in this study are off and physician choice on patient care reigns. It the past few years there have been a lot of studies on what addition drug agents might help GBM patients. I'm not an oncologist, but I wager if I know as a layman what drugs to try, so do they. If I know that departure from Stupp is helpful (greater than 6 cycles) so do they. And they will know that once their patients crossover they are on vaccine. Knowing this, surgeons will opt to do surgery and remove additional mass if they can. And they will introduce other chemo drugs in a newly diagnosed environment (mass removed) along with the vaccine. And while some may not believe it, there's enough research evidence that dendritic cell vaccine are synergistic with chemo agents. Crossover patients, who previously were in the treatment arm (blinded), in theory can end up having a second PFS event (or not, depending how effective the vaccine is against their disease). There are a number of dendritic cell immunotherapy trials waiting to see what happens with this one. If not for nothing, lots of information will be gathered from it.
Maybe the regulators will say "no more changes", that's always possibility. I believe that is what was meant by their risk disclosure. Koman seems convinced that the company will not be able to continue to treat patients until the end of the study without recruiting again. I'm not sure I agree with that. If they're over 300-patients, then there's no reason why the regulators just let the study meet its final endpoint and the OS results age and the regulators to decide if the vaccine is contributing to life-extension or not.
As for HE, they won't be able to accept nGBM patients until this Phase III closes recruitment. That isn't my opinion, that's HE rules.
AI
