RE:RE:RE:RE:RE:RE:RE:New PR Announcing Initiation of Basket Trial That's probably right --not enough patients on long enough and having done the proper scans. I've relegated learning anything about efficacy to the basket trial a while ago. I was hoping that with some sort of data around the plasma readings, some safety data, simple things like survivability (how long the longest person was on in 1a), etc... might shed some light on POC issues. But that will all have to wait.
My view is to try to comp this in-line with other ADC/oncology trials. THere are a lot that have wacky-type issues you would have to disclose (being out of the ordinary) even in a dosage trial. So just the fact that they can now say they are done -- they've completed a "safe" (definied within the FDA concepts for oncology dosage trials) cycle on 6 patients is at least positive compared to some other trials. Is it all that helpful to us for eliminating downside probabilities-- not really as you all are pointing out. We can probably assume 3 of those patients are past 1 cycle and may be on to 2/3/4 at this point. Reason being they have said they would roll some patients into 1b and they are confirming today that the basket trial has started. So how many of them are in the cancer types they want is the question.
Like JFm has pointed out, this part of the trial THTX can take more control over which patients fit through all the filters they have now imposed --it is NOT all-comers anymore (except for that amorphous 15 patients in "various" other tumors types group).
My net/net is that this didn't really eliminate the downside case probabilities because of the limited data coming out around POC issues. The positive is that they have confirmed a large dose, once again mentioned it will be "multiplied" by some factor which they don't really know at this point and could only guess at anyway in this phase. But as opposed to some that start their efficacy trials knowing there will be a few serious side-effects they need to counter or really monitor for, they haven't mentioned anything with those 6 patients. There could be something (we should assume that at some point cumulative toxicity will appear and have some of the normal taxol issues), but it may still allow longer dosing --at least that's the hope. So I'm just relating this starting point for the basket trial to others we've seen where they are starting their first widespread efficacy trials with more serious hair around them. There just may be hair around this, but I guess it's not big enough (yet) to be material to starting 1b and moving it up one step.
Another point would be that if any of those first 3 patients are still on, then they will fall into the 1b protocol which specifies RECIST readings and scans. In other words, they should have some preliminary signs (maybe not enough for a proper PR level) for a few patients in 4 cycles; so anywhere from 6 to 12 weeks. I would think they will have at least something to say in the July/Aug timeframe for a tiny, anecdotal episode. Then we can see if this PDC works and the concept is valid. Until then, the downside was not eliminated with this release unless we learn from PL and CM over the next 4-6 weeks if they do a conference or something.
qwerty22 wrote: You don't have to suppose about the dose for the expansion phase, it's 300. That's a reasonably good outcome. I think Wino said he was relatively confident they would show that. I wasn't given the trouble they had at 420. That's a small win today.
It good to try to ask why they didn't give us any more detail today. I have a simple answer. They don't have a clear, reportable efficacy signal yet. Without that reporting the details would most be reporting toxicities. There is other stuff that we would all be interested in reading but in the context of some toxicities and no efficacy it probably raises as many questions as it answers. So that's my best explanation for them not revealing anything much other than what is necessary for them to tell us the expansion phase is starting.
There's more pessamistic reads from today along the lines that they have stuff they want to hide. Somebody else can talk about that if they want.
The next big question is why don't they have an efficacy signal. The horrible thing to say, after waiting all this time, is likely it's still to early. I'm working on a maximum of 13 evaluable patients from 1a. Some of them may have dropped out both reaching 2 scans (4 cycles) which would be the minimum for a truly reportable, solid efficacy signal. The last six patients probably aren't at that point just because not enough time has passed. Given we can rule out efficacy at lower doses then the pool of patients from which you might get a reportable efficacy signal is tiny at this point in time.
I hate that they are telling us nothing but in the scenario were they have no efficacy signal it's probably the best thing to do. Trying to dig into data that lacks an efficacy signal is most likely just going to look like trying to polish a turd. And I don't think they have a turd (not yet anyway).
Biobob wrote: You can suppose what you want ... they leave all the possibilities ot suppositions open to us so we can continue to suppose.. I suppose.