RE:RE:Thyroid cancerAgain. They explained that they go based on probability that a cancer type will overexpress sortilin based on analysis of hundreds of tumor biopsies by a technique called tissue microarray. These biopsies are not those of actual patients, they are just a samples they bought somewhere. They think these samples are representative of the different cancer types at large, but even in this experiment, they don't get 100% of individual tumors with sortilin overexpression. They get a percentage of a given tumor type overexpressing sortilin to some extent. So, the idea based on that is to go with probability, but again, the probability is not 100%, and also, overexpression can go from low to very high. So the idea is probably that among the 70 patients they will enroll, they will have enough with some sortilin overexpression to show if the concept works.
https://www.geneticistinc.com/blog/traditional-biopsy-techniques-vs-tissue-microarray-1
The strange thing is that at some point they said that they would test single patients for sortilin overexpression but not as a selection criteria. I don't know what is the plan about that. Do they intend to test only patients where the drug showed efficacy? I don't know. The sortilin status of patients is critical in the hope of efficacy, it is also critical to demonstrate clearly a proof of concept, but they don't talk about it, they don't clearly explain themselves about that, and analysts in conference calls are too incompetent to ask a specific questions about it, and insist on it if they try to elude the questions. So that's where we are at this point. In a trial on a targeted drug with no assessment of the target and a company that avoid to talk about it.
Two weeks ago I got a cancer treatment with a targeted drug, a PDC, Lu177-Dotatate, and I wrote here that before injecting me the drug the doctor in charge told me that they were giving me this drug because a recent Ga68-Dotatate SPECT scan showed that my tumors were still catching the imaging PDC, a proof that they would also catch the treatment PDC because I still had somatostatin receptors overexpression, and because of that they thought that this treatment would still be beneficial to me. Three days after treatment I had a follow up scan to see if the drug indeed went into my tumors, and it did. Then the doctor explained to me that it was very good, that the tumors were still catching a high amount of the PDC. I spoke 30 minutes with him asking many questions, and at some point he told me that as long as all my tumors, which are all metastatic tumors, the primary cancer has been removed surgically. So, as long as all my tumors would overexpress the somatostatin receptor, thus, bind the PDC, they would continue, periodically, to treat me with Lu177-Dotatate. But he also told me, when one of the tumor will mutate and will no longer overexpress the somatostatin receptor, they would stop giving me this targeted drug and that I would have to switch to something else like chemotherapy. In other words, for him it would be pointless to treat a patient with a PDC, even if only one of tens of tumors was not overexpressing the target.
Again. I understand that in my case we talk about a drug with a long track record, especially in Europe. We also talk about a drug with an imaging companion where only the radioisotope is different. So it is very easy to monitor everything with high precision. I understand that Thera are not there yet, in fact, they are very far away from that, but it does not prevent them from better explaining their approach to this question. If the goal is to establish a proof of concept, they will have no other choice than to directly assess sortilin expression level in relation with efficacy. So why are they not doing it as a screening criteria to treat? I know they work with fragile very advanced patients on which making a biopsy could be problematic, but still, it's a targeted drug. At some point they will need to assess sortilin overexpression directly. So why can't they explain clearly the way they are doing it or plan to do it?
PWIB123 wrote: So, what are we missing? Would THTX be able to set up eronious trials with the FDA's blessing? The specific cancers had to have been chosen for a reason, right? What's the typical protocol on something like this? Is it normal to test specific cancers just to see what happens when the entire premise of the peptide was to seek out sortilin? I get the "all comers". I don't get the specific cancers that don't over express sortilin. What might THTX know that we don't know?
jfm1330 wrote: It is so boring to follow Thera, no news, nothing, that I found a link saying that Thera was recruiting patients with thyroid cancer and also anaplastic thyroid cancer.
https://www.medifind.com/articles/clinical-trial/239307806
I was surpised by this distinction, so I made a little bit of research on anaplastic thyroid cancer (ATC) and sortilin expression. I ended up with a relatively recent article from 2172 stating that sortilin is not overexpressed at all in anaplastic thyroid cancer and that there was low to very low overexpression in two other types of thyroid cancers, follicular thyroid carcinoma (FTC) and papillary thyroid carcinoma (PTC). Baseline expression in non cancerous thyroid tissues is around 15, ATC 24, FTC 29.7, and PTC 40.8. Important to note that the article defines high sortilin overexpression at 100 or higher. So all these thyroid cancers types seems to be nowhere near high overexpression.
Again. I don't see how they can enroll patients in phase Ib without histological determination of real sortilin overexpression. Based on what the released publicly, this is the enormous weakness of this trial. How would you convince a patient with thyroid cancer to enroll in this trial if he would be aware of those numbers? Only out of total despair.
https://ajp.amjpathol.org/article/S0002-9440(17)30492-3/fulltext