RE:RE:RE:RE:RE:RE:AACR Poster - very interesting An "interim read" would be a great way to understand the pause if that was what it was. It makes everything fall into place. We are still left with the fact that they concluded part 2 had a high probability of not reaching the goal that was set for it but it might put to bed some of the very negative options that have been going through my head.
I'm liking that as a jumping off point to understand the pause.
Wino115 wrote: I've thougth about that question too and knowing these things are always data driven, it seems to point to that. I've assumed some of the logic was that it showed very positive pre-clinical efficacy and safety, there's some sense with the very long SDs and PRs that conceptually it's getting there, but it's no where near the results to move it further.
They basically came to the same conclusion some of you all did a long while ago, while all-comers is a way to learn a lot about sort1 expression, efficacy, safety and where and why it may work in certain areas, it's also a more expensive approach and more the realm of larger trials backed with a ton of money. If you dont' fit that category, and THTX did not, it's 100% dependent on getting some element of efficacy seen in the P1 part. The big boys can literally just look for safety, tolerability and a RP2D and probably would have been fine with large SDs and a couple PRs and then done something larger and smarter in P2 --they can afford that. THTX had no luxury and the wick was burning low. THere was no way they were going to get there unless everything worked perfectly as in mice, and the chances of that were lowered as it went on.
But, not lowered enough given you added 40 weeks to someones life that was likely ending in a few, to not reset it to target where some efficacy was seen, right patient types at baseline, right tumor type, right sub-type, do the tests, play with a few dose/timing schedules, and look to magnify those small signs you saw to see 1 or 2 CRs or a bunch of PRs and keep those SDs as they are also telling around safety. Was there a rationale to think it could be? I guess the SAC was tasked with that job. Nothings perfect in these trials with loads of pure experimentation as Juniper always said. If they can do testing, which we'll hear about, then they are doing half of what the science guys here wanted to see (unfortunately the chemo can't be changed at this point). Let's see how strongly they are filtering the enrollee part versus basically no filtering before. We'll see if they have added in biopsy and have the money/time for that. Would be the way to do it, so we'll find out.
It disappointed in a population group where it didn't do what they theorized well enought to warrant any more investment. The interim read showed it wasn't worth doing the same thing, but the question the SAC and investigator had to answer was, is the full set of data showing enough probable conclusions that we can extrapolate some theories on what we're seeing to slightly shift the probabilities around more focused enrollees and tumor types, plus how to balance that need for cell death versus tolerability to get ORRs into the right categories and high enough percentages that it may help this status of cancer patient where nothing else is working? It's a hurdle for sure given those 18 patients so the question is, since they won't enroll 18 patients like that again, will the next 18 based on those criteria and various dosing options increase tumor shrinkage form single digits to 30% or more. They would need 2-3 of those SDs to hit a positive endpoint of being a RECIST PR. Not easy, and let's see if they can convince us that is in the cards on their science day. I hope they bring in some of those SAC members for that call given their level of expertise --a docetaxol expert, a PDC expert and a TNBC expert, plus the lead investigator if they can get her.