RE:RE:RE:RE:RE:RE:RE:RE:RE:News out 👀Trodelvy had some fairly serious safety issues it had to overcome. At one point, they delayed the trial as the FDA had some issues with it. So they had a very extended timeline from P1 to commercialization.
The good thing for TH1902 is that the hardest part is often safety and, cross-fingers, it has so far shown fairly modest safety and tolerability issues. It seems some of the pre-clinical was close to what they've seen and, importantly, not much at all gets in the blood system and causes neutropenia. It was more the normal things with targeted cancer drugs -- tingling (neuropathy), rash, runs, nausea, eye dryness, etc... Nothing very life threatening or that would stop treatment (at this 300mg level). I hope I'm not whistling past the graveyard and they've now found tons of new safety issues, but the fact Patient 2 took it for 33 weeks and didn't die (and most were large doses) is a good indication. That's like 10-11 treatments, which is very large cumulatively.
I think we're learning that they could have gone a bit faster in 1a but likely pushed the investigators to keep trying at 460mg. That and the safety investigation likely added a few months. Now we're in the P1b and need to see where they are. I was guessing about half way through enrollment which assumes it takes them 3-4 weeks to get an enrollee in it, some drop out, the possibly required safety balancing as QWERTY explained, etc... Maybe it could have happened faster, but it doesn't seem like it can with the competition with other ADCs, combo drugs and the THTX lack of clinical reputation for oncology. We'll get there. We just have to hang in there.
LouisW wrote: I took Trodelvy as an example. Their PhI tested 25 patients and was initiated on Dec 17th 2012. I cannot find when they completed the PhaseI study but their Phase I data was published on September 2015.
Okay. TH1902 is testing the performance on 88 patients (1a:18+ 1b:70). The intiattion date was Mar 2021 and target to end the study at the end of Q1 2023. So to consider the study size and the timeline, i dont really think TH1902 is slower. Again, if the Phase I target to test on patients, it is impposible to complete the study within one year.
PWIB123 wrote: Everything I've read says that Ph.1 oncology trials usually last between several months to no more than 1 year. I think everyone here has thought through every possibility as to why it has taken so long and come up with a number of plausible explanations, but it is odd that the company has never addressed the timing. Maybe it's because they feel they are still within the reset timeline or they are afraid it will make them look bad if they address it directly. I kind of wonder if we should expect longer timelines due to this being such a novel approach. Do we know if this is in line with others ADC's or PDC's doing something similar? I don't have enough background to know where to compare. If everyone else is blowing through Ph. 1 in 3 months and moving on to Ph. 2, then maybe that is a reflection of our leadership.
jeffm34 wrote: They are now 20 months into the Phase 1 trial and they are still using pre clincial studies to try and validate the platform. This poster should have been highlighting some patient specific data from the trial.
jfm1330 wrote: The big takeaway from this poster is the fact that cancer stages don't matter much for many cancers tested. Also, it does not solve anything related to the proof of concept. We are still swimming in hypothetic stuff. As long as we don't have the proof of concept, all that and the preclinical work and any ideas about new PDC could be worthless. It would also have been interesting to know what was the scores all of their different types of grafted tumors on nude mice that they used for preclinical work. This would have given a better understanding of how it could translate to humans. Also, remember that this is in vitro testing where the tissue is chemically treated before and after staining, how would these results correlate with in vivo testing of receptor expression like it is the case with Dotatate Ga68 for example. Also, how would it compare with gene expression testing for sortilin.
Add to that the fact that membrane sortilin can be cleaved to generate soluble sortilin. Another thing is turnaround of outside cell membrane sortilin. We know there is intracellular sortilin related to membrane organelles lile Golgi apparatus and endoplasmic reticulum and there is a recuperation cycle associated with that. So in vitro staining is a snapshot of sortilin presence on the outside cell membrane, while the in vivo process is dynamic with sortilin coming in and going out of the outside membrane. All that to say that this is a very little piece of the puzzle, and not a crtitical one in my view. We desperately want to see data strongly hinting at a proof of concept. I know I insist a lot of that, but it is obviously critical for the whole thing.
Now we have TH1902, a PDC that is a candidate drug, proof of concept gives you a platform. With proof of concept it would no longer be only about TH1902. In other words, if docetaxel is not good enough as a cytotoxic agent, you can go with another one. Yes there would be big delays in that case, but still, you have a valid approach. If the concept is invalid, it's the end of everthing. That's why it would be so important to have that. Until we have this critical milestone, we are in the world of hypotheses. Without proof of concept, total failure of the SORT1+ plarform is a possibility. With proof of concept the question becomes how good can it be? Is TH1902 the best possible PDC out of that platform, etc... I know it's early. I know they cannot answer all the question at once, but at the same time they are so slow in the clinical trial and so secretive