RE:RE:RE:Had a thoughtOne more thing, even though the study is for "all comers", I think they can still select patients to have the right balance between those overexpressing sortilin and those who don't. We already know that some advanced cancer have 90% of patients overexpressing sortilin. So just by selecting patients with these type of cancer, chances are very high they will have patients overexpressing sortilin in the phase Ia. I think they really want to come out of phase Ia with some positive efficacy data. That's why we will likely see results only in 2022.
jfm1330 wrote: With Trodelvy having 33% response rate and 45% clinical benefit rate (those with at least stable disease for at least 6 months), there is still many TNBC patients with overexressed sortilin available for the phase Ib and also for a possible phase II.
The remaining question at this point, given the dose they are at in the phase Ia right now (likely twice the MTD of docetaxel alone), is if the linker is working as planned, so allowing selective cleavage inside sortilin expressing cells, and bypassing of MDR efflux pump. The other concern, is the number of taxane resistant patients in these advanced cancer patients with no other valid options.
If TH1902 works as planned, will it allow to overcome taxane resistance? In the Trodely trial, 98% of the patients enrolled were taxanes resistant. So resistant to taxanes injected under the free form. Animal model showed that TH1902 is more effective than docetaxel injected alone, but these tests were made on commercial TNBC cells. Will it be the same on real big heterogenous tumors? For sure it won't work on 100% of the TNBC/sortilin+ patients. We don't need that, not even close. But we need it to work on some, and obviously, the higher the percentage of responders, the better it would be.
My hope at this point lies on the dose they are at right now (likely twice MTD of docetaxel). Also the fact that Marsolais said that what they see is similar to what they saw on animals in the preclinical work, and Levesque saying that the level of free docetaxel they see in the blood of patients after injection with TH1902 is very low, similar to the preclinical data he showed in his presentation.