Theratechnologies Inc T.TH

Dose Escalation Question

[Wino115]

Simple question on Patient #1, do they escalate the dosage for each patient or do you keep the dose constant for each patient, so Patient #2 will get the higher dosage while Patient #1 sticks at the original dose level?

From the description, it looks like the former but it's not entierly clear the way it's worded.  So Patient #1 if he passed the exam, got a higher dosage for his second round.  Patient #2 will start at the same beginning dose and then also escalate.  Is that correct?

From the clinical trial site:

" Dose escalation by dose-doubling will be done for the first 2 dose levels, followed by a modified Fibonacci dose escalation scheme (i.e. dose increases of 67%, 50%, 40% and 33%) thereafter for each dose level. Patients in Part 1 will be observed for 21 days post Cycle 1 Day 1 drug administration for dose limiting toxicity (DLT). Dose escalation to the next dose level will proceed following satisfactory review of safety data until the MTD is reached. The MTD is defined as that dose-level at which ≤1 of 6 patients in a cohort develop an emergent DLT."

[juniper88]

Patient #2 will go to the next higher dose. Patient # 1 will never go higher than patient #2. Both will continue to go up as the trial proceeds.

[Wino115]

Got it - so they all escalate, but never higher than the newest patient's dosage. So if we have no Patient #2 yet, the Gettysburg patient is still at the original dosage level.   I guess we don't have a way to know if anyone else has enrolled except if the company gives an update. I would have thought it wouldn't be hard to identify possible patients given it's a refractory

[realitycheck4u]

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[Wino115]

I've never seen it for every patient, but sometimes companies will provide updates with regular quarterly updates or when some meaningful target is reached, like "all-filled", or last patient for the Phase 1 reached, etc... Maybe they'll be more proactive in their quarterlies with broad trial updates, but don't expect hard data until end of Part 1.  I wouldn't mind

[qwerty22]

I believe Paul said at that recent investor conference that the 1st patient had just received their second dose. Those types of off the cuff statements until something material happens would be fine with me. Reality I think it's unlikely they give us a running commentary of each patient.

[SPCEO1]

That is correct Qwerty. Someone earlier said something about a third dose but Paul said it was a second dose. Has it seemed to take longer than expected to put the second dose into the first patient? If so, does anyone have any theories as to why it took longer than three weeks to administer the second dose?  And does anyone know how many doses the first patient will get before the second

[qwerty22]

Unfortunately the bloom burton presentation is gone now (another aspect of the company really not caring about their messaging) but I believe what he said was the 2nd dose had happened earlier that week or the previous week (I forget which). I think when I tried extrapolating back it seemed to fit the right timetable (1st dose announcement 23rdMarch). The person talking about the 3rd dose is

[scarlet1967]

As per the company the study will use a modified rapid dose-escalation design as described by Simon et al. (1997). Looking through the article below they might stay with one patient only (not traditional 3+3 escalation design), doubling the dose until the patient shows DLT, which can reduce the duration of the trial etc.   “Design 1 was a conventional design (similar to the commonly used

[qwerty22]

The trial expects 65 patients and part 2 accounts for 40 so that leaves 25 for dose escalation. I don't know how that fits with any of these designs. I'm not worrying at all about the cancer program, it seems on track atm.

[scarlet1967]

That's correct, my point was it looks like they can keep dosing the first patient until they show toxicity then they go back to original design with 3 to 6 patients will be dosed. If that's their approach it might be longer time than classic design before they move on to the second, third etc patients.   "Design 2 treats one patient per dose level until one patient exhibits

[scarlet1967]

My understanding is they have now dosed the first patient twice and they can keep dosing the same patient until they show DLT then they use the data and go back to design 1(traditional 3+3 design) thus less patients are unnecessary exposed to very low dosing and they save some time as well. This might explain why the second patient hasn't been dosed. below is the original design 1 procedure.

[AMoschitto]

Sorry to add any confusion--was just trying to estimate the third dose. Glad to hear if it hasn't happened yet, we are close. Thanks for the correction. 

[SPCEO1]

I am not super familiar with how other companies handle this, but you can be sure different companies do it differently. CYDY will no doubt put out a press release highlighting that their first TNBC patient brushed her teeth this morning, therefore she is alive and you should buy their stock. TH has always been at the opposite end of the spectrum when it comes to disclosures like this and I am not

[stockman75]

Is there anything that prevents the doctor from Gettysburg providing an update on patient 1 or other patients? Some type of legal agreement where he is restricted in what information he can share? It seems based on the past report the doctor is not shy sharing updates and if things were going absolutely fantastic and he was at liberty I wouldn't be suprised to see another update.

[SPCEO1]

I am just guessing but it makes sense to me that Dr. Shah would have had to get permission to do that interview. I know someone who contacted the newspaper who did the story and they said it was their hope to do a follow-up 60-90 days after the original story. We will have to see if that happens.  

[jeffm34]

Would be nice if maybe some local Canadian media picked up on the story as well. Interview the physician and the patient like the other news article did. Get people excited about a local company with a potential break through cancer treatment.

[qwerty22]

It seems like it's a big deal for that smaller cancer center and local media. I was hoping the media would want to do a follow up on that patient just from the human interest angle so it's pleasing you say this. It's so, so early in the trial though we shouldn't be expecting too much at this stage but best of luck to the guy.

[qwerty22]

I think that's right, patient 1 will escalate alongside patient 2. I think there's some strong assumption that the first dose is below the efficacy level of the drug (that might not be true though). It seems to me there would be an aspect of cruelty to keeping the first patient on that dose through all their dosings.  

[AMoschitto]

So Patient 1 in Gettysburg (being first dosed in early March) has probably had their 3rd dose.* So this would be the 3rd dose on the escalation schedule, is that right? *3rd dose assumes the 3 week dosing schedule that Dr. Shah mentions in the article. 

[ANALIAS00]

The way I understood from M. Dubuc is that first patient received a very very light dosage so they can evaluate the side effect. The second patient was supposed to receive the double dose of what the first patient received. The third patient should receive the double dose of what the second patient received and so on until they find and determine the best dosage for all based on side effect. That