RE:RE:RE:RE:Silver liningNot hear to debate since the situation is as it is at the moment. But it seems to me that since the situation around safety was not the normal problem with docetaxal you would see (severe neutropenia) that the issue may not be the free float level of 10% being much higher than they state, but that sort1 is more prevalent in the two areas mentioned (ocular/extremity nerves) and it's being absorbed there causing issues. They specifically stated it was just those two areas and neutropenia was not mentioned as a limiting factor they considered. According to CMO, they saw low levels in bone marrow readings (mentioned at one point). To be fair, it would be worth clarifying that around any new data gleened by CMO.
Given ADCs have similar issues evidently, it could be something else instead of sort1 levels, but could be addressed with the lower more frequent approach.
Nonetheless, they do need to provide more context and explanation on the reset. The sooner the better. I think the normal way to deal with safety issues is to play with the dose like they are, but they need to discuss the efficacy portion and why they think frequency is the answer to what they observed and what dose can work. Maybe like you say, they're playing with a weaker warhead in a tough stage of cancer to fight and there's better, but that's for another day. Get the concept working first if you can! CEO, CMO at a minimum should put something together and go out to the market with a more indepth discussion or call to talk it through and provide needed insights so we can recalibrate and they reset the trial.
jfm1330 wrote: Fooled again by this company.
Forget the 4-7 x dose. In ligth of the actual situation, this is very unlikely. And again, the 10% of free docetaxel they claim, we don't know what it is. With the toxicity we see, it is likely that it is more than 10% of the dose injected. Also, I never like docetaxel as a warhead, not powerful enoufgh and too much resistance to it in advanced patient. Also, we pay for the non testing of patients for sortilin overexpression as a criteria for enrollment. We are so far from proof of concept, and again, the company decided to not release any data that would allow me to think the problem is dosing. Again, they inject only 30% more than the MTD of docetaxel alone. So the toxicity problem raise doubts about the validity of TH1902 entering cells expressing sortilin in humans. Also, when they will restart the trial, it will be hard to enroll patients. With what we know now, would you be willing to enroll in this trial? We understand now why enrollment was so sluggish.
Wino115 wrote:
They have room to play with dosage levels given it concentrates the normal dose 4-7x, so theoretically you could cut the dose in half and go more frequently and still deliver 2-4x the normal dose and that could go a long way toward eliminating side effects but getting the chemo directly in. In hindsight, it probably would have been worth trialing a large dose at 3 weeks and a half dose at 8 days and see which gives you better parameters. That's essentially what they're planning on doing now.