RE:RE:RE:RE:RE:Combo tests with anti PD-L1 chekpoint inhibitors To me two experimental drugs in a combo trial is not a great way to go. It looks an ugly bet. How do you untangle the contribution of each drug to the toxicity signals? Or efficacy signals? It seems to me to bring far more disadvantages than advantages.
I was drawn to a little comment by FM-B. Towards the end, when talking about the protocol changes, she noted disparagingly that two variables were being changed in the new protocol. That points to me how little tolerability these investigators have for change or too many unknowns floating around. I don't think any of us think the present changes any big deals but clearly for her each change has significance and too much change has consequences. In some ways I see Theratech taking half a step backwards with these changes. They are back to looking at dose escalation. Not as onerous as the first time but it's there. That must be in part due to the fact that there is new uncertainty about exactly how the toxicity profile will pan out with the new protocol. Enrolment also looks very tightly controlled resumably for the same reasons. My guess is introduce more changes, such as the ones some here are calling for and eff3ctiv3ly you end up taking full steps backwards to the start and for the regululators it begins to look like a full reset. I think these are some of the real-world limitations that many of us, including me, don't always consider when we go off on our flights of fancy. The company are far more anchored by reality than us, that's a good thing.
I was struck just how much Christian wanted to emphasis that every change they have made to the protocol is supported by their observational data, unfortunately he didn't go into all the detail and I'm sure some of the observations are more weighty than others but that is at the heart of their process. It's not always such a consideration for some of us at times.
Wino115 wrote: Interesting thoughts, indeed. I've also thought that it doesn't necessarily need to be one of the existing PD-L1 therapy companies that woudl be interested --of course, they should be as if it works it would propel your therapy into uncharted cold tumor territory. But it would be most appealing for someone looking to get into the immuno-oncology field with a more unique and differentiated approach that would allow them to capture the expanded IO cold tumor market all to themselves. If it's the same size as the hot tumor market, then they have $30bil to go for!
You'll recall that a quick search I did found there were something like 30 or so companies developing PD-a and PD-L1 therapies. There were an equal number in China alone. They're really focusing on expanding the immuno-oncology field there. I don't think it would even cost you a whole lot to do a combo trial.
I guess one of your points is that you'd want to use an approved PD-L1 to make the trail "easier", and that makes sense. Play the two sides off each other and go for the best deal! Time for these boys to get out there and really push super hard for something with that IO finding. Even Dr. Meric-B mentioned it as one of the juggerrnauts in oncology drugs.
One last. tidbit -- I assume that whole presenation was done with LifeSci Advisors filling in. I thought that was a pretty slick overall webcast and done with out an in=house IR person. A few screw-ups with the person hitting the slides not always knowing it was adding an element to a slide and not moving to the next slide. But I think that only happened once with Marsolais.